Method and system for providing a personalized cannabinoid treatment regimen

ABSTRACT

Methods and systems for providing a personalized cannabinoid treatment regimen to a patient include obtaining genotypes of single nucleotide polymorphisms (SNPs) from a patient&#39;s genetic test and modifying base values, such as base dosages or base ratios, using weighting values reflecting the obtained genotypes to obtain regimen values for treating the patient. The regimen values take into account expected responses to cannabinoids based on patient genetic information.

SEQUENCE LISTING

The instant application contains a Sequence Listing which has beensubmitted electronically in ASCII format and is hereby incorporated byreference in its entirety. Said ASCII copy, created on Dec. 23, 2019, isnamed GDNA-1-1001_SL.txt and is 17,458 bytes in size.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application claims the benefit of U.S. Provisional PatentApplication Ser. No. 62/786,158, filed Dec. 28, 2018, which isincorporated herein by reference in its entirety.

FIELD

The present invention is directed to the area of methods and systems fordetermining and providing treatment parameters for use of cannabinoids.The present invention is also directed to methods and systems forutilizing patient DNA information to provide personalized cannabinoidtreatment regimen.

BACKGROUND

Over 100 chemically and biosynthetically related cannabinoids, and wellover 100 terpenes, have been identified in cannabis to date. Many of thecompounds have been shown to have therapeutic or health-relatedbenefits.

There are two major cannabinoids, cannabidiol (CBD) andΔ⁹-tetrahydrocannabinol (THC), along with several other less potentcannabinoids, such as cannabichromene (CBC), cannabichromevarin (CBCV),Δ⁹-tetrahydrocannabivarin (THCV), cannabigerol (CBG), cannabigerovarin(CBGV), cannabidivarin (CBDV), and cannabinol (CBN).

THC shows wide clinical benefit for symptoms of diseases such as energymetabolism, pain and inflammation, neuroprotection, Alzheimer's disease,Huntington's disease, anxiety and fear, sleep disorders, emesis,gastrointestinal disorders, cardiovascular disorders, cancer, and so on.A synthetic analog of THC, nabilone, was approved for the suppression ofthe nausea and vomiting caused by chemotherapy.

CBD is anxiolytic, antidepressant, antipsychotic, anticonvulsant,antinausea, antioxidant, anti-inflammatory, antiarthritic, andantineoplastic. Within the central nervous system (CNS) it is effectivein animal models of epilepsy, anxiety, psychosis, and diseases of thebasal ganglia, such as Parkinson's and Huntington's diseases, and CBDalso shows beneficial effects in treatments of psychosis, epilepsy,anxiety, sleep, neuroprotection and neurodegenerative diseases, such as,Alzheimer's disease, Parkinson's disease, and Huntington's disease,pain, inflammation, autoimmunity, and retinal diseases, emesis, cancer,and so on.

Of the less potent cannabinoids there are many investigations whichdemonstrate that at least some of the therapeutic benefits of THC andCBD are also available from a handful of other cannabinoids, such as,CBC, CBG, CBDV, THCV, Δ⁹-tetrahydrocannabinolic acid (THCA), andcannabidiolic acid (CBDA). For example, the US National Academy ofSciences, Engineering and Medicine (NASEM) reported clinical evidence ofan effect on chronic pain and good evidence of an effect on anxiety andsleep disturbance (i.e. insomnia).

BRIEF SUMMARY

One embodiment is a method of providing a personalized cannabinoidtreatment regimen to a patient. The method includes obtaining two ormore base values, wherein each of the base values is a different one ofthe following: a) a base dosage for a first cannabinoid; b) a basedosage for a second cannabinoid; c) a base dosage for a combination ofthe first and second cannabinoids; or d) a base ratio of the first andsecond cannabinoids; for each of a plurality of single nucleotidepolymorphisms (SNPs) in a selected set of SNPs, obtaining, from agenetic test of the patient, a genotype for the SNP; for each of theSNPs in the selected set of SNPs, obtaining, for the obtained genotypeof the SNP, at least one weighting value which reflects, for theobtained genotype of the SNP, one or more responses selected from thefollowing: i) a response to the first and second cannabinoids; ii) aresponse to the first cannabinoid only; iii) a response to the secondcannabinoid only; or iv) cannabinoid dependency; modifying the two ormore base values based on the obtained weighting values to produce twoor more regimen values, wherein each of the regimen values is adifferent one of the following: a) a regimen dosage for the firstcannabinoid; b) a regimen dosage for the second cannabinoid; c) aregimen dosage for a combination of the first and second cannabinoids;or d) a regimen ratio of the first and second cannabinoids; and treatingthe patient using the first and second cannabinoids according to the twoor more regimen values.

In at least some embodiments, the first cannabinoid is cannabidiol (CBD)and the second cannabinoid is Δ⁹-tetrahydrocannabinol (THC). In at leastsome embodiments, the method further includes obtaining a condition fortreatment, wherein the selected set of SNPs includes a plurality of SNPsassociated with the condition. In at least some embodiments, a value ofat least one of the base values is dependent on the condition. In atleast some embodiments, the condition is selected from pain, depression,anxiety, fear, sleep disorder, insomnia, energy metabolism disorder,inflammation, neuroprotection, Alzheimer's disease, Huntington'sdisease, Parkinson's disease, emesis, gastrointestinal disorder,cardiovascular disorder, cancer, nausea, vomiting, epilepsy, psychosis,diseases of the basal ganglia, neurodegenerative diseases, autoimmunedisorder, retinal diseases, arthritis, convulsions, neoplastic diseases,or any combination thereof.

In at least some embodiments, modifying the two or more base valuesincludes modifying at least one of the base values by multiplying the atleast one of the base values by a product of at least one of theweighting values for each of a plurality of the SNPs.

In at least some embodiments, obtaining at least one weighting valueincludes obtaining the weighting values for each of the followingresponses individually: i) the response to the first and secondcannabinoids, ii) the response to the first cannabinoid only; iii) theresponse to the second cannabinoid only, or iv) the cannabinoiddependency. In at least some embodiments, modifying the two or more basevalues includes modifying at least one first value, selected from thetwo or more base values, using the weighting values for a first one ofthe responses to produce at least one first intermediate value;modifying at least one second value, selected from the two or more basevalues and the at least one first intermediate value, using theweighting values for a second one of the responses to produce at leastone second intermediate value; modifying at least one third value,selected from the two or more base values, the at least one firstintermediate value, and the at least one second intermediate value,using the weighting values for a third one of the responses to produceat least one third intermediate value; and modifying at least one fourthvalue, selected from the two or more base values, the at least one firstintermediate value, the at least one second intermediate value, and theat least one third intermediate value, using the weighting values for afourth one of the responses to produce at least one of the regimenvalues.

In at least some embodiments, obtaining the two or base values includesdetermining the two or more base values using at least one factorselected from patient weight, condition for treatment, patient age,patient gender, patient body type, other medications taken by patient,or results of a patient blood test.

Another embodiment is a system for providing an individualizedcannabinoid treatment regimen. The system includes a processorconfigured to perform actions to produce the individualized cannabinoidtreatment regimen, the actions including: obtaining two or more basevalues, wherein each of the base values is a different one of thefollowing: a) a base dosage for a first cannabinoid; b) a base dosagefor a second cannabinoid; c) a base dosage for a combination of thefirst and second cannabinoids; or d) a base ratio of the first andsecond cannabinoids; for each of a plurality of single nucleotidepolymorphisms (SNPs) in a selected set of SNPs, obtaining, from agenetic test of the patient, a genotype for the SNP; for each of theSNPs in the selected set of SNPs, obtaining, for the obtained genotypeof the SNP, at least one weighting value which reflects, for theobtained genotype of the SNP, one or more responses selected from thefollowing: i) a response to the first and second cannabinoids; ii) aresponse to the first cannabinoid only; iii) a response to the secondcannabinoid only; or iv) cannabinoid dependency; and modifying the twoor more base values based on the obtained weighting values to producetwo or more regimen values, wherein each of the regimen values is adifferent one of the following: a) a regimen dosage for the firstcannabinoid; b) a regimen dosage for the second cannabinoid; c) aregimen dosage for a combination of the first and second cannabinoids;or d) a regimen ratio of the first and second cannabinoids.

In at least some embodiments, the first cannabinoid is cannabidiol (CBD)and the second cannabinoid is Δ⁹-tetrahydrocannabinol (THC). In at leastsome embodiments, the actions further include obtaining a condition fortreatment, wherein the selected set of SNPs includes a plurality of SNPsassociated with the condition. In at least some embodiments, modifyingthe two or more base values includes modifying at least one of the basevalues by multiplying the at least one of the base values by a productof at least one of the weighting values for each of a plurality of theSNPs.

In at least some embodiments, obtaining at least one weighting valueincludes obtaining the weighting values for each of the followingresponses individually: i) the response to the first and secondcannabinoids, ii) the response to the first cannabinoid only; iii) theresponse to the second cannabinoid only, or iv) the cannabinoiddependency. In at least some embodiments, modifying the two or more basevalues includes modifying at least one first value, selected from thetwo or more base values, using the weighting values for a first one ofthe responses to produce at least one first intermediate value;modifying at least one second value, selected from the two or more basevalues and the at least one first intermediate value, using theweighting values for a second one of the responses to produce at leastone second intermediate value; modifying at least one third value,selected from the two or more base values, the at least one firstintermediate value, and the at least one second intermediate value,using the weighting values for a third one of the responses to produceat least one third intermediate value; and modifying at least one fourthvalue, selected from the two or more base values, the at least one firstintermediate value, the at least one second intermediate value, and theat least one third intermediate value, using the weighting values for afourth one of the responses to produce at least one of the regimenvalues. Another embodiment is a non-transitory processor readablestorage media that includes instructions for producing an individualizedcannabinoid treatment regimen, wherein execution of the instructions byone or more processors cause the one or more processors to performactions, including: obtaining two or more base values, wherein each ofthe base values is a different one of the following: a) a base dosagefor a first cannabinoid; b) a base dosage for a second cannabinoid; c) abase dosage for a combination of the first and second cannabinoids; ord) a base ratio of the first and second cannabinoids; for each of aplurality of single nucleotide polymorphisms (SNPs) in a selected set ofSNPs, obtaining, from a genetic test of the patient, a genotype for theSNP; for each of the SNPs in the selected set of SNPs, obtaining, forthe obtained genotype of the SNP, at least one weighting value whichreflects, for the obtained genotype of the SNP, one or more responsesselected from the following: i) a response to the first and secondcannabinoids; ii) a response to the first cannabinoid only; iii) aresponse to the second cannabinoid only; or iv) cannabinoid dependency;and modifying the two or more base values based on the obtainedweighting values to produce two or more regimen values, wherein each ofthe regimen values is a different one of the following: a) a regimendosage for the first cannabinoid; b) a regimen dosage for the secondcannabinoid; c) a regimen dosage for a combination of the first andsecond cannabinoids; or d) a regimen ratio of the first and secondcannabinoids.

In at least some embodiments, the first cannabinoid is cannabidiol (CBD)and the second cannabinoid is Δ⁹-tetrahydrocannabinol (THC). In at leastsome embodiments, the actions further include obtaining a condition fortreatment, wherein the selected set of SNPs includes a plurality of SNPsassociated with the condition.

In at least some embodiments, obtaining at least one weighting valueincludes obtaining the weighting values for each of the followingresponses individually: i) the response to the first and secondcannabinoids, ii) the response to the first cannabinoid only; iii) theresponse to the second cannabinoid only, or iv) the cannabinoiddependency. In at least some embodiments, modifying the two or more basevalues includes modifying at least one first value, selected from thetwo or more base values, using the weighting values for a first one ofthe responses to produce at least one first intermediate value;modifying at least one second value, selected from the two or more basevalues and the at least one first intermediate value, using theweighting values for a second one of the responses to produce at leastone second intermediate value; modifying at least one third value,selected from the two or more base values, the at least one firstintermediate value, and the at least one second intermediate value,using the weighting values for a third one of the responses to produceat least one third intermediate value; and modifying at least one fourthvalue, selected from the two or more base values, the at least one firstintermediate value, the at least one second intermediate value, and theat least one third intermediate value, using the weighting values for afourth one of the responses to produce at least one of the regimenvalues.

BRIEF DESCRIPTION OF THE DRAWINGS

Non-limiting and non-exhaustive embodiments of the present invention aredescribed with reference to the following drawings. In the drawings,like reference numerals refer to like parts throughout the variousfigures unless otherwise specified.

For a better understanding of the present invention, reference will bemade to the following Detailed Description, which is to be read inassociation with the accompanying drawings, wherein:

FIG. 1 is a block diagram of one embodiment of a computing system forpracticing the invention;

FIG. 2 is a flow chart of one embodiment of a method of producing anindividualized cannabinoid treatment regimen, according to theinvention;

FIG. 3 is a flow chart of one embodiment of a method of modifying basevalues using weighting values to obtain regimen values, according to theinvention;

FIG. 4 is a flow chart of another embodiment of a method of modifyingbase values using weighting values to obtain regimen values, accordingto the invention;

FIG. 5 is graph of different health conditions for participants in astudy;

FIG. 6 is a graph of cannabis dosage versus body weight for theparticipants in the study based on conventional dosage determinations;and

FIG. 7 is a graph of cannabis dosage versus body weight for theparticipants utilizing patient DNA information to provide a personalizedcannabinoid treatment regimen, according to the invention.

DETAILED DESCRIPTION

The present invention is directed to the area of methods and systems fordetermining and providing treatment parameters for use of cannabinoids.The present invention is also directed to methods and systems forutilizing patient DNA information to provide personalized cannabinoidtreatment regimen.

In at least some embodiments, the systems and methods described hereincan utilize a computer system for determining recommended regimen valuesfor treatment using two or more cannabinoids. FIG. 1 is a block diagramof components of one embodiment of such a computer system 100. Thecomputer system 100 can include a computing device 120 or any othersimilar device that includes a processor 122 and a memory 124, a display126, and an input device 128.

The computing device 120 can be a computer, tablet, mobile device, fieldprogrammable gate array (FPGA), or any other suitable device forprocessing information. The computing device 120 can be local to theuser (such as a clinician or patient) or can include components that arenon-local to the user including one or both of the processor 122 ormemory 124 (or portions thereof). For example, in at least someembodiments, the user may operate a terminal that is connected to anon-local computing device. In other embodiments, the memory 124 can benon-local to the user.

The computing device 120 can utilize any suitable processor 122including one or more hardware processors that may be local to the useror non-local to the user or other components of the computing device.The processor 122 is configured to execute instructions provided to theprocessor 122.

Any suitable memory 124 can be used for the computing device 120. Thememory 124 illustrates a type of computer-readable media, namelycomputer-readable storage media. Computer-readable storage media mayinclude, but is not limited to, nonvolatile, non-transitory, removable,and non-removable media implemented in any method or technology forstorage of information, such as computer readable instructions, datastructures, program modules, or other data. Examples ofcomputer-readable storage media include RAM, ROM, EEPROM, flash memory,or other memory technology, CD-ROM, digital versatile disks (“DVD”) orother optical storage, magnetic cassettes, magnetic tape, magnetic diskstorage or other magnetic storage devices, or any other medium which canbe used to store the desired information and which can be accessed by acomputing device.

Communication methods provide another type of computer readable media;namely communication media. Communication media typically embodiescomputer-readable instructions, data structures, program modules, orother data in a modulated data signal such as a carrier wave, datasignal, or other transport mechanism and include any informationdelivery media. The terms “modulated data signal,” and “carrier-wavesignal” includes a signal that has one or more of its characteristicsset or changed in such a manner as to encode information, instructions,data, and the like, in the signal. By way of example, communicationmedia includes wired media such as twisted pair, coaxial cable, fiberoptics, wave guides, and other wired media and wireless media such asacoustic, RF, infrared, and other wireless media.

The display 126 can be any suitable display device, such as a monitor,screen, or the like, and can include a printer. In some embodiments, thedisplay is optional. In some embodiments, the display 126 may beintegrated into a single unit with the computing device 120, such as atablet, smart phone, or smart watch. In at least some embodiments, thedisplay is not local to the user. The input device 128 can be, forexample, a keyboard, mouse, touch screen, track ball, joystick, voicerecognition system, or any combination thereof, or the like. In at leastsome embodiments, the input device is not local to the user.

In at least some embodiments, the systems and methods described hereincan provide personalized information, such as personalized treatmentregimen values including personalized dosages, that can facilitate, oreven accelerate, an individual's treatment or path to wellness usingcannabinoids, the medicinal compounds produced from cannabis and hemp.In at least some embodiments, the systems and methods utilize personalgenetic information to estimate how an individual's endocannabinoidsystem may be predisposed to function in response to cannabinoids. Thisinformation can facilitate a better understanding of the potentialefficacy of cannabinoid dose regimes for the relief of conditionsincluding, but not limited to, pain, depression, anxiety, fear, sleepdisorder, insomnia, energy metabolism disorder, inflammation,neuroprotection, Alzheimer's disease, Huntington's disease, Parkinson'sdisease, emesis, gastrointestinal disorder, cardiovascular disorder,cancer, nausea, vomiting, epilepsy, psychosis, diseases of the basalganglia, neurodegenerative diseases, autoimmune disorder, retinaldiseases, arthritis, convulsions, neoplastic diseases, or the like.

The human endocannabinoid system includes receptors, enzymes, andproteins that process cannabinoids as well as other compounds that canregulate or otherwise affect aspects of human health and wellbeing. DNAencodes the genetic information to produce these receptors, enzymes, andmetabolic proteins and there is substantial variance between individualswith respect to the DNA sequences for these genes. This natural geneticvariation can affect how the endocannabinoid system functions in eachperson. The DNA variation can be determined by DNA sequence analysis toprovide an overview of the genetic composition of the genes involved inthe perception and response to cannabinoids.

Knowledge of individual endocannabinoid system, based on personalgenetic information, can be used to provide insights as to the potentialresponse to particular dose regimes of cannabinoids to treat, forexample, conditions such as pain, depression, anxiety, fear, sleepdisorder, insomnia, energy metabolism disorder, inflammation,neuroprotection, Alzheimer's disease, Huntington's disease, Parkinson'sdisease, emesis, gastrointestinal disorder, cardiovascular disorder,cancer, nausea, vomiting, epilepsy, psychosis, diseases of the basalganglia, neurodegenerative diseases, autoimmune disorder, retinaldiseases, arthritis, convulsions, neoplastic diseases, or the like.According to a 2016 WebMD survey, 48% of medical cannabis patients takebetween 3 to 6 months or longer, and spend up to $3,000, to find theappropriate cannabinoid combination to address their condition. Thesystems and methods described herein can be used to facilitateefficiently identifying a dosage, and ratio, of CBD and THC or othercannabinoids to treat a desired condition or conditions based on patientgenetic information.

Studies of THC lead to the discovery of a cannabinoid receptor, CB1, andthe human endocannabinoid system (ECS). In at least some embodiments,the ECS is defined as the ensemble of: a) two 7-transmembrane-domain andG protein-coupled receptors (GPCRs) for THC—cannabinoid receptor type 1(CB1) and cannabinoid receptor type 2 (CB2); b) two endogenous ligands,the “endocannabinoids” N-arachidonoylethanolamine (anandamide) and2-arachidonoylglycerol (2-AG); and c) the enzymes responsible for a)endocannabinoid biosynthesis (includingN-acyl-phosphatidyl-ethanolamine-selective phospholipase D (NAPE-PLD)and diacylglycerol lipases (DAGL) a and 13, for anandamide and 2-AG,respectively) and b) hydrolytic inactivation (including fatty acid amidehydrolase (FAAH) and monoacylglycerol lipase (MAGL), for anandamide and2-AG, respectively).

Endocannabinoids and the ECS can regulate synaptic plasticity in thecentral nervous system to modulate brain functions such as memory, moodand emotions, and pain perceptions. The ECS may promote bothnon-rapid-eye movement and rapid-eye-movement sleep by interacting withmelanin-concentrating hormone neurons in the lateral hypothalamus.

THC and THCV bind with high affinity to CB and CB2 (with agonist andantagonist activity for THC and THCV, respectively). CBD, on the otherhand, may indirectly affect CB1/CB2 by weakly inhibiting AEA enzymatichydrolysis (for example, inhibiting FAAH) to regulate the ECS and effectthe pain, anxiety, and insomnia conditions. Cannabinoids also exhibitmoderate activity on a wide array of molecular targets (for example,orphan GPCRs) including several channels belonging to the transientreceptor potential (TRP) family, such as rat and human transientreceptor potential vanilloid subtype 1 channel (TRPV1),5-hydroxytryptamine receptors (5-HT) (for example, HT1A or serotoninreceptors) to modulate brain functions (for example, pain perceptions).

The therapeutic efficacy of cannabinoids may be impacted by geneticvariations of the receptor genes (CB1, CB2, TRPV1, and HT1A), thetransport genes (ATP-Binding Cassette Subfamily B member 1 (ABCB1),Solute Carrier Family 6 member 4 (serotonin transporter) (SLC6A4)); themetabolism genes (Cytochrome P450, CYP2C9 and CYP3A4, andCatechol-O-Methyltransferase (COMT)), as well as interactions of thegenetic variations between these genes. Pharmacogenomic andpharmacogenetic test-guided target therapy, as described herein, canprovide a cost-effective approach to personalized treatments, and isparticularly attractive for complex diseases or disorders for which itis often difficult to tailor treatments (for example, pain, depression,anxiety, fear, sleep disorder, insomnia, energy metabolism disorder,inflammation, neuroprotection, Alzheimer's disease, Huntington'sdisease, Parkinson's disease, emesis, gastrointestinal disorder,cardiovascular disorder, cancer, nausea, vomiting, epilepsy, psychosis,diseases of the basal ganglia, neurodegenerative diseases, autoimmunedisorder, retinal diseases, arthritis, convulsions, neoplastic diseases,or the like). Chronic pain, anxiety, depression, and sleep disorders areused herein as examples.

Chronic pain is one example of a malady which may be treated by medicalcannabis. There is substantial clinical evidence that cannabis is aneffective treatment for chronic pain, often with fewer side effectscompared to opioids. It is believed that endocannabinoids localizethroughout the brain and activate CB1 and TRPV1. It is believed thatstimulation of CB1 can exert anti-inflammatory and analgesic effects,whereas TRPV1 activation may increase inflammation, pain and feverthrough the enhancement of neurotransmitter release and the secretion ofpro-inflammatory cytokines.

Genetic variations of cannabinoid receptors (CB1 and CB2), the principlecannabinoid catabolic enzyme (FAAH), the transport gene (ABCB1), and themetabolism genes (COMT and Cytochrome P450, CYP2C9 and CYP3A4) mayresult in different gene expression levels or activity in response tocannabinoids, as well as different levels of association to multipledrug dependence and adverse drug reactions (ADRs). For example,variations in TRPV1 have been associated with higher pain tolerance orhigher risk of interferon-induced side effects in patients with multiplesclerosis. Genetic variations of the transport gene (ABCB1) and themetabolism genes (COMT and Cytochrome P450, CYP2C9 and CYP3A4) have beenassociated with drug efficacy and ADRs in pharmacogenomic studies.Identification of these genetic variations in an individual can be usedto make recommendations to the individual with respect to the safety andefficacy of personalized cannabis use in pain management or othertreatments.

Excessive fear and anxiety are symptoms of a number of neuropsychiatricdisorders including generalized anxiety disorder (GAD), panic disorder(PD), and social anxiety disorder (SAD). The endocannabinoid system(ECS) can modulate synaptic plasticity that affect learning and responseto emotional salient and aversive events. It is believed that activationof CB1 can produce anxiolytic effects and produce negative feedback tothe neuroendocrine stress response. It is believed that chronic stressimpairs ECS signaling in the hippocampus and amygdala and can lead toanxiety. It is believed that genetic variants of CB1 and FAAH in ECS arelinked to high anxiety, particularly when interacting with genevariations in other systems, such as the serotonin transporter gene(SLC6A4), or with early life stress.

Cannabis use demonstrates a level of efficacy for anxiety reduction instudies. Anxiety may also be partially regulated by serotonin levels forwhich a number of currently available pharmacological treatments weredeveloped, such as selective serotonin reuptake inhibitors (SSRIs),serotonin-norepinephrine reuptake inhibitors, benzodiazepines, monoamineoxidase inhibitors, tricyclic antidepressant (TCA) drugs, and partial5-HT_(1A) receptor agonists. in particular. Genetic variations in thefollowing genes have been shown to affect therapeutic efficacy andantidepressant (AD) response: SLC6A4, Serotonin Receptor 1A and 2A(HTR1A and HTR2A), Brain Derived Neurotrophic Factor (BDNF), and COMT.By genetic testing of these AD response gene variants along with thegeneric variants of CB1 and FAAH genes of the ECS and Cytochrome P450genes that catabolize cannabis and antidepressants, a personalizedanxiety/depression treatment recommendation for CBD and THC use can berendered, as described herein.

Insomnia is a common sleep disorder and while its cause is often unknownit may often be a consequence of a chronic disease associated withstress, pain, or depression. It is believed that administration ofcannabinoids can be an effective treatment as THC has been found topromote sleep in both humans and animals. Further, CB₁ activation maylead to induction of sleep in a manner blocked by a selective CB1antagonist. Genetic variants of FAAH were found to be associated withpoor sleep quality.

Genetic variants of the 33 subunit of the GABA_(A) receptor and theserotonin transporter are associated with insomnia. Currently, drugtreatments of insomnia include classes of antagonists of histamine H1receptors such as diphenhydramine; low-dose doxepin (a TCA with highaffinity for the H1 receptor); Mirtazapine (an antidepressant with 5-HTand His antagonistic properties); benzodiazepines (BZD) andnon-benzodiazepine agonistic allosteric modulators of GABA_(A)receptors; and exogenous melatonin. Genetic variants affecting exposureand sensitivity to drugs that improve sleep include the isoenzymes ofCytochrome P450s such as CYP2D6, CYP1A2, CYP2C9, and CYP2C19; the HTR1Band HTR2A genes, and the melatonin receptor genes (MTNR1A). Genome-wideassociation analysis of insomnia complaints identified one high risklocus—MEIS 1. Personalized insomnia therapy based on CBD and THC use canbe recommended by testing these gene variants, as described herein.

Genetic testing can be utilized to investigate single nucleotidepolymorphisms (SNPs) of interest in genes associated with the ECS.Tables 1 to 4 provide examples of SNPs of interest relating to cannabisresponse (Table 1), pain treatment (Table 2), anxiety/depression (Table3), and sleep disorders/insomnia (Table 4). As an example of the methodsand systems, after analyzing the SNPs of interest in genes associatedwith the ECS, 38 SNPs of high potency, as determined by publishedstudies, were selected and are presented in Tables 5A and 5B. PCRamplification and Next Generation Sequencing (NGS) sequencing primerswere designed to investigate these SNPs.

It will be understood, however, that other selections of SNPs can beused. Moreover, SNPs may be selected based on factors such as, thecondition being treated, whether cannabinoid dependency is to beinvestigated, the potency of SNP variation, and the like.

In one example, PCR primers were designed using the Primer3plus platform(available at https://primer3plus.com/), although any other suitablemethod of primer design can be used. Examples of primers are presentedin Table 5 below. The PCR primers were obtained from Integrated DNATechnologies, Inc. (Skokie, Ill., United States) after adding propersequence adaptors for NGS sequencing. In this example, using one controlhuman DNA sample as the template, PCR amplification showed all amplifiedunique products. In this example, nine PCR products were larger than theexpected size, which is not unexpected due to continuous updating ofhuman genome sequencing and SNP annotations.

In this example, the PCR products were sequenced under MiSeq System(Illumina, San Diego, Calif., United States) and analyzed. High qualitygenome sequence coverages (the number of sequence reads per SNP) wereproduced, and 34 of the SNPs were successfully read through the SNPgenome locations with NGS sequence read coverages from 348 to 11,263 asshown in Table 6A. Minor mutation alleles were identified from 18 SNPsas shown in the “Mutation Call: Relative to CDS” column in Table 6B.

Over the 100 chemically and biosynthetically related cannabinoids thathave been identified in cannabis to date, the two major components,cannabidiol (CBD) and Δ⁹-tetrahydrocannabinol (THC), are widely adoptedin the treatment and clinical studies with various dosages and ratiosfor different conditions. There are many different factors that can playa part in the effectiveness and user experiences of cannabis treatments.These include, but are not limited to, a) the symptoms or conditions tobe treated, b) the intensity or progressiveness of the system orcondition, c) individual biology and metabolism, d) the individual'sendocannabinoid system and how it reacts to CBD and THC, e) body weight,f) individual sensitivity to cannabis compounds, g) other medicationsbeing taken, and h) daily food intake patterns including the quantityand quality of the food.

A common conventional practice to determine the dosage and ratio of CBDand THC begins with the lowest dosage and increases the dosage every twoto four days based on the effects on the user. This process may takemonths and cost thousands of dollars before finding an appropriatedosage and ratio for a user's condition, for example, pain,anxiety/depression, insomnia, or the like, as well as the THC dependenceof the user.

The methods and systems described herein utilize a pharmacogenomicsapproach and facilitate estimation of dosage and ratio of CBD and THCfor treatment of a condition and, at least in some instances, alsoaccount for THC dependence. The systems and methods use geneticvariations in the endocannabinoid systems to account for the impact inthe responses to CBD and THC or other cannabinoids.

The systems and methods described herein can utilize any combination ofthe genes and SNPs described above or any other genes and SNPs. Thesystems and methods utilize a selected set of SNPs that containsmultiple SNPs. In some embodiments, the systems and methods may utilizea selected set of SNPs regardless of the condition to be treated. Inother embodiments, some or all of the SNPs in the selected set of SNPsmay be selected based on the condition to be treated. In at least someembodiments, the number or identity of the SNPs in the selected set ofSNPs may be modified by factors such as, for example, the condition tobe treated, the results of a genetic test (for example, if the genotypeof a SNP is not sufficiently determined), or the like or any combinationthereof. As an example, from the 19 genes, 38 SNPs, 108 genotypes of the38 SNPs, as well as five haplotype SNPs from CNR1, GABRA2, and MAPK14genes, as presented in Tables 1 to 4, a selection of 38 SNPs ispresented in Tables 5A, 5B, and 6. Table 7 also presents the differentalleles for each SNP.

FIG. 2 is a flow chart for one method of determining regimen values fortreating a patient. The methods and systems described herein willdescribe treatment using two cannabinoids as an example and, inparticular, will describe treatment using CBD and THC as an example. Itwill be understood, however, that the systems and methods describedherein can be utilized for determining regimen values, such as dosage orratio of CBD to THC, and treatments using one, two, three, four, or morecannabinoids and using cannabinoids other than CBD or THC.

In steps 202, two or more base values are obtained. Examples of basevalues include the following: a) a base dosage for a first cannabinoid,such as CDB, b) a base dosage for a second cannabinoid such as THC, c) abase dosage for a combination of the first and second cannabinoids (forexample, CDB and THC), or d) a base ratio of the first and secondcannabinoids (for example, CBD/THC). In one embodiments, the method orsystem uses a starting CBD dosage, a starting THC dosage, and a startingCBD/THC ratio (or any two of these base values).

The base values can be selected using any suitable method including, butnot limited to, published recommendations, clinician experience, publicresearch studies, other data, or the like. The base values may take intoaccount one or more factors, such as, but not limited to, condition tobe treated, age, body weight, gender, body type, other medications,results of blood tests or other tests, or the like or any combinationthereof. As an example, in one embodiment, for starting CBD and THCdosage and CBD/THC ratio, published recommendations in Leinow andBirnbaum. CBD, A Patient's Guide to Medical Cannabis (North AtlanticBooks, Berkeley, Calif., 2017—incorporated herein by reference in itsentirety) were used as a middle point base dosage (D1—Table 9) and ratio(R1—Table 9) after factoring the medical conditions, age, and bodyweight of the patient.

In step 204, a genotype for each SNP in a selected set of SNPs isobtained from a genetic test of the patient. As indicated above, the setof SNPs may be any suitable set of SNPs or may include SNPs selectedspecifically for the condition to be treated. Any suitable method can beused for determining the genotype including, but not limited to, PCRamplification and sequence determination. Table 8 presents one exampleof a set of SNPs and a corresponding allele, determined from a genetictest, for each of the SNPs.

In step 206, one or more weighting values are obtained based on thegenotypes of the SNPs. Each of the weighting values reflects, for theobtained genotype of the SNP associated with the weighting value, one ormore responses selected from the following: i) a response to the firstand second cannabinoids (for example, CBD and THC); ii) a response tothe first cannabinoid only (for example, CBD only); iii) a response tothe second cannabinoid only (for example, THC only); or iv) cannabinoiddependency (i.e., a likelihood for developing dependency on a drug suchas, for example, THC). Table 8 presents one example different weightingvalues for the determined allele for each of the SNPs (see columnslabeled “Cannabis Dosage”, CBD Dosage”, “THC Dosage” and “DrugDependence (THC)”). Table 7 presents one example of weighting values foreach of the alleles for each SNP (see columns labeled “Cannabis Dosage”,CBD Dosage”, “THC Dosage” and “Drug Dependence (THC)”). In thisillustrated embodiment, differences in weighting values were made in0.25 increments, but it will be understood that other arrangements ofweighting values can be determined with different in increments of 0.01,0.05, 0.10, or the like or any other suitable increment.

In at least some embodiments, the weighting value is in the range of 0to 5 or more or the range of 0 to 2 or more. In these embodiments, theweighting values may multiple the base value (or an intermediate value)to modify the base value (or intermediate value) as illustrated in theexamples below. Thus, a weighting value of 1 indicates that theparticular genotype associated with that weighting value is not expectedto have an effect on the base value. In contrast, a weighting value ofless than 1 for a base value related to dosage may indicate that, forthe patient's genotype, the cannabinoid may have larger than averageeffect, thereby suggesting that a lower dosage is recommended.Similarly, a weighting value of more than 1 for a base value related todosage may indicate that, for the patient's genotype, the cannabinoidmay have smaller than average effect, thereby suggesting that a higherdosage is recommended.

The weighting values also reflect, in part, the use of a productfunction, as described below. It will be understood that otherfunctions, such as a summation function or an exponential function, maybe used which would then incorporate a different range for the weightingvalues. In some embodiments, the weighting values may also be presentedas a percentile or fraction.

The weighting values can be selected based on literature studies,practitioner experience, public research studies, or other data, or thelike or any combination thereof. Moreover, the weighting values may alsotake into account one or more factors, such as, for example, patientweight, patient gender, or the like or any combination thereof.

As an example, in at least some embodiments, the individual weightingvalues for each of the SNPS are determined using one or both of thefollowing: 1) direct evidence of increasing or decreasing gene activityor treatment response to multiple drugs (for example, in one embodiment,the SNP variants from COMT, CYP2C9, CYP2C19, ABCB1, or HTR2A genes wereevaluated based on this evidence) or 2) indirect evidence of increasingor decreasing of gene expressions, which typically leads to increased orreduced activity or responsiveness under cannabinoid treatments (forexample, in one embodiment, the SNP variants CNR1, CNR2, HTR1A, HTR2A,AKT1, NRG1, or FAAH genes were evaluated based on this evidence).

In step 208, the weighting values are used to modify the base values inorder to generate two or more regimen values. The regimen values can be,for example, a) a regimen dosage for the first cannabinoid (for example,CBD), b) a regimen dosage for the second cannabinoid (for example, THC),c) a regimen dosage for a combination of the first and secondcannabinoids (for example, CBD or THC), or d) a regimen ratio of thefirst and second cannabinoids (for example, CBD/THC). In at least someembodiments, a report is provided to the patient or a clinician with theregimen values. The modification of the base values using the weightingvalues may include generating intermediate values and may include two ormore substeps (examples provided below in the description of theflowcharts of FIGS. 3 and 4).

The modification of the base values, based on the weighting values,personalizes the treatment for the patient based on the patient'sgenetic information. The weighting values are used to personalize thetreatment by accounting for the patient's genotypes in the selected setof SNPs. As an example, as indicated above, in some embodiments, theweighting values range from 0 to 2 or more and are used as a multiplierfor the base value (or other intermediate value) to generate the regimenvalues. A specific example of one embodiment of this modification methodis provided below. It will be understood, however, that othercalculational methods for modification can be used including, but notlimited to, summation of weighting values, averaging of weightingvalues, or the like. In such cases, the weighting values are likely tobe given a different range of possible values.

In step 210, the patient can be treated using the regimen values. Asindicated above, the regimen values personalize the treatment. It willbe understood, however, that these regimen values may simply be astarting point for the treatment and further modifications may be madeover time based, for example, on patient experience with the treatment,worsening or improvement of the condition, changes in medical situation(which may impact overall health), age, weight, or the like or anycombination thereof.

One or more weighting values can be associated with the genotype of eachSNP. For example, the genotype of each SNP may have a single weightingvalue associated with that genotype to represent the general response ofa patient with that genotype to cannabinoids.

Alternatively, multiple (for example, two, three, four, or more)weighting values can be associated with at least some (or even all) ofthe SNPs and their genotypes. Such an arrangement can be used to accountfor different types of impact. For example, different weighting valuesmay be provided for each of the following four different responses (orany subset of these four responses): i) a response to the first andsecond cannabinoids (for example, CBD and THC); ii) a response to thefirst cannabinoid only (for example, CBD only); iii) a response to thesecond cannabinoid only (for example, THC only); or iv) cannabinoiddependency (i.e., a likelihood for developing dependency on a drug suchas, for example, THC). In at least some embodiments, a weighting valuefor each of these responses is provided for each genotype of each SNP.Alternatively, only a subset of the SNPs may be considered for each typeor response and, therefore, weighting values for that type or responseare provided for only that subset of SNPs.

As an example, in at least some embodiments, different types of impactof these variant SNP genotypes to the cannabis (CBD+THC) dosage andCBD/THC ratio can be considered. For example, Type I SNP genotypesrespond differently to both THC and CBD. In one embodiment, 16 Type ISNP genotypes were identified, as illustrated in Table 7. It will berecognized, however, that other embodiments may include more or fewerType I SNP genotypes.

As another example, Type II SNP genotypes respond differently to CBDonly. In one embodiment, 5 Type II SNP genotypes were identified, asillustrated in Table 7. It will be recognized, however, that otherembodiments may include more or fewer Type II SNP genotypes.

As a further example, Type III SNP genotypes respond differently to THConly. In one embodiment, 10 Type III SNP genotypes were identified, asillustrated in Table 7. It will be recognized, however, that otherembodiments may include more or fewer Type III SNP genotypes.

Type I, Type II, and Type III SNP genotypes, alone or in combination,may lead to reduced or increased overall dosage of cannabis (CBD+THC)and the ratio of CBD and THC in the treatments of conditions. The rateof dosage change from some genotypes provides a direct impact, whereasothers may produce an indirect impact to gene expression and enzymaticactivity.

As yet another example, Type IV SNP genotypes are associated with THCdependence only. In one embodiment, 13 Type IV SNP genotypes wereidentified, as illustrated in Table 7. It will be recognized, however,that other embodiments may include more or fewer Type IV SNP genotypes.These SNP genotypes may lead to reduced or increased THC dosage. In atleast some embodiments, analysis of Type IV SNP genotypes may result inincrease or reduction of the ratio of CBD to THC but not the overallcannabis (CBD+THC) dosage in the treatments (see, for example, Table 7).

As described above, the base values are then modified by taking intoaccount one or more of the four types of SNP genotypes to estimateunique individual genetic impacts of CBD and THC (or other cannabinoids)to arrive at suggested regimen CBD and THC dosages and a regimen CBD/THCratio based on patient DNA tests.

FIG. 3 illustrates one embodiment of a method for modifying base valuesusing weighting values (for example, step 208 in FIG. 2) using the fourtypes of SNP genotypes. In step 302, at least one of the base values ismodified using the weighting values for a first type of SNP genotype(for example, the Type I SNP genotypes described above) to produce atleast one first intermediate value. In step 304, at least one base valueor first intermediate value is modified using the weighting values for asecond type of SNP genotype (for example, the Type II SNP genotypesdescribed above) to produce at least one second intermediate value. Instep 306, at least one base value or first or second intermediate valueis modified using the weighting values for a third type of SNP genotype(for example, the Type III SNP genotypes described above) to produce atleast one third intermediate value. In step 308, at least one base valueor first, second, or third intermediate value is modified using theweighting values for a fourth type of SNP genotype (for example, theType IV SNP genotypes described above) to produce at least one regimenvalue.

The flowchart in FIG. 3 illustrates a process for four types of SNPgenotypes, but it will be understood that the process can be readilycontract for two or three types of SNP genotypes by removing one or twosteps or expanded for four or more types of SNP genotypes by addingsteps similar to steps 304 or 306.

FIG. 4 illustrates one embodiment of a process that implements the stepsof FIG. 3 (steps 404 to 416) using the four types of SNP genotypesdescribed above and provides an example of specific equations that canbe used in this embodiment. It will be understood that these equationsare examples and that other methods of modifying the base values toobtain the regimen values can be used. Table 8, below, provides anexample of SNP genotypes and weighting values. Table 9, below, providesone specific case of determined SNP genotypes with the correspondingweighting values.

In step 402, specific base values (a base CBD+THC dosage and a baseCBD/TCH ratio) are obtained. In the equations below, D1 is the baseCBD+THC dosage and R1 is the base CBD to THC Ratio, which are obtainedin step 402 (see, also step 202 described above).

In step 404, the base CBD+TCH dosage is modified based on the Type I SNPgenotypes to obtain a first intermediate CBD+TCH dosage. In at leastsome embodiments, D2 is the first intermediate CBD+THC dosage afterfactoring the individual impact of the obtained Type I SNP genotypesfrom the genetic test of the patient's DNA. D2 can be determinedaccording to the following equation:

${D\; 2} = {D\; 1{\prod\limits_{i = 1}^{n}a_{i}}}$

where

n=the number of Type 1 SNP genotypes tested and considered,

i=individual Type 1 SNP genotype, and

a_(i)=weighting value of the Type I SNP genotype i.

Alternatively, instead of limiting the calculation of D2 to Type I SNPgenotypes, weighting values of all of the SNP genotypes can be used. Itis likely, however, the weighting values of SNP genotypes other than theType I SNP genotypes will have a value of 1 or a value near 1.Similarly, other steps described below include calculations using one ofthe types of SNP genotypes, but these steps can also be modified toinclude the weighting values for all of the SNP genotypes. In addition,as indicated above, in other embodiments, a summation function orexponential function can be used instead of the product functionpresented herein. This is also applicable to other equations presentedbelow.

In Step 406, C2, the first intermediate CBD dosage after factoring theindividual impact of Type I SNP genotypes, is determined according tothe following equation:

${C\; 2} = {D\; 2( \frac{R\; 1}{{R\; 1} + 1} )}$

Also, T2, the first intermediate THC dosage after factoring theindividual impact of Type I SNP genotypes is determined according to thefollowing equation:

${T\; 2} = \frac{D\; 2}{{R\; 1} + 1}$

In step 408, the impact of the Type II SNP genotypes is introduced. C3,the second intermediate CBD dosage after factoring the individual impactof Type II SNP genotypes is given by the following equation:

${C\; 3} = {C\; 2{\prod\limits_{i = 1}^{n}b_{i}}}$

where

n=the number of Type II SNP genotypes tested and considered,

i=individual Type II SNP genotype, and

b_(i)=individual impact of the Type II SNP genotype i.

In step 410, T3, the second intermediate THC dosage after factoring theindividual impact of Type II SNP genotypes, is given by the followingequation:

${T\; 3} = {T\; 2{\prod\limits_{i = 1}^{n}c_{i}}}$

n=the number of Type III SNP genotypes tested and considered,

i=individual Type III SNP genotype, and

c_(i)=individual impact of Type III SNP genotype i.

In step 412, D3, the second intermediate CBD+THC dosage after factoringthe individual impact of Types I-III SNP genotypes, is given byD3=C3+T3.

In step 414, the impact of the Type IV SNP genotypes is considered. T4,the regimen THC dosage after factoring the individual impact of Type IVSNP genotypes, is given by the following equation:

${T\; 4} = {T\; 3{\prod\limits_{i = 1}^{n}d_{i}}}$

n=the number of Type IV SNP genotypes tested and considered,

i=individual Type IV SNP genotype, and

d_(i)=individual impact of the Type IV SNP genotype i.

These calculations then lead to the following dosages and ratios:

C4 is the regimen CBD dosage after factoring the individual impact ofType IV SNP genotypes and is given by: C4=D3−T4

R_(f) is the regimen CBD to THC ratio after factoring the impact of SNPgenotypes and is given by: R_(f)=C4/T4

D_(f) is the regimen CBD+TCH dosage after factoring the impact of SNPgenotypes and is given by: D_(f)=C4+T4.

Table 9 illustrates the base, intermediate, and regimen values for threeexamples of different treatments.

The final recommendations of the CBD+THC dosage and the CBD to THC ratiocan be provided to a clinician or patient in, for example, a report orrecommendation card. In at least some embodiments, details of the SNPgenotypes (e.g., genetic variants) and their impacts on the dosage andratio may also be delivered to a clinician or patient in the same ordifferent report.

Example

Selected variants and the algorithm were used to predict the CBD/THCdosage in treating different conditions or combinations of differenthealth conditions including pain, anxiety, and insomnia. Samples wereobtained from participants who were exploring cannabis solutions toresolve either the individual conditions of pain (P), anxiety (A), orinsomnia (I), or combinations of these individual conditions:pain/anxiety (P/A), pain/insomnia (P/I), anxiety/insomnia (A/I), or allthree conditions (P/A/I). FIG. 5 shows the number of donors showinginterest in each one of these health conditions.

Saliva samples were processed for DNA preparation, PCR and sequencing,and for the subsequent identification and analysis of the gene variants.The variant Linkage Disequilibrium and the genotype association to thehealth conditions was analyzed as illustrated in FIG. 6. LinkageDisequilibrium (LD) tests (see Reference 53) verified several groups ofassociated variants from common genes (e.g. variant rs 2229579,rs35761398, and rs2501432 from the CNR2 gene; rs279871, rs279856, andrs279826 from the GABRA2 gene; and rs806368, rs12720071, and rs1049353from the CNR1 gene) as well as associated variants from different genes(e.g. rs12199654 from MAPK14 and rs12720071 and other SNP variants fromCNR1) indicating high quality variant genotype data were generated inthis study. A number of variants were associated with statisticalsignificance with pain and with other health conditions suggestinghighly quality genetic variants were selected in this study (see, Table10 below).

In addition to the variants demonstrating association to differenthealth conditions, a number of different variants that may impact thereception, signaling, as well as metabolism of cannabinoids, and thuslead to different dosage requirement for individuals were alsoidentified from every saliva sample (see Table 11 that presents examplesof variant alleles identified from two saliva samples 1002 and 1013).

To determine the dosage of cannabis, it is a common practice to start byweighting in body weight and different health conditions of concern.Conventionally, larger body weight leads to an increase in dosage,whereas different health conditions also result in variation of thedosage for a given body weight. As an example, conventionally, amicro-dose is considered effective for insomnia, but a standard tomacro-dose may be recommended for pain and anxiety conditions. For the19 participant samples analyzed in this Example, standard doserecommendations for their different body weight and different healthconcern are presented in FIG. 6.

In contrast, a genotyping procedure, as described herein, identified aunique set of 5 to 12 variants, see Table 12, likely impacting thecannabis dosage for each participants. The genetic impact of thevariants on the dosage of CBD and THC were calculated using thealgorithm described above. Results, presented in FIG. 7, showed highlydifferentiated and personalized CBD/THC dosage comparing to the standarddose recommendations, suggesting that this selected group of variantsand the dosage calculating algorithm is a useful approach to predictingthe CBD/THC dosage for the health conditions described here. Afterdelivering the genetic report and dosage recommendation to the salivadonors, follow-up interviews all returned positive feedbacks from thesedonors.

It will be understood that each block of the flowchart illustrations,and combinations of blocks in the flowchart illustrations and methodsdisclosed herein, can be implemented by computer program instructions.These program instructions may be provided to a processor to produce amachine, such that the instructions, which execute on the processor,create means for implementing the actions specified in the flowchartblock or blocks disclosed herein. The computer program instructions maybe executed by a processor to cause a series of operational steps to beperformed by the processor to produce a computer implemented process.The computer program instructions may also cause at least some of theoperational steps to be performed in parallel. Moreover, some of thesteps may also be performed across more than one processor, such asmight arise in a multi-processor computer system. In addition, one ormore processes may also be performed concurrently with other processes,or even in a different sequence than illustrated without departing fromthe scope or spirit of the invention.

The computer program instructions can be stored on any suitablecomputer-readable medium including, but not limited to, RAM, ROM,EEPROM, flash memory or other memory technology, CD-ROM, digitalversatile disks (“DVD”) or other optical storage, magnetic cassettes,magnetic tape, magnetic disk storage or other magnetic storage devices,or any other medium which can be used to store the desired informationand which can be accessed by a computing device.

The above specification provides a description of the manufacture anduse of the invention. Since many embodiments of the invention can bemade without departing from the spirit and scope of the invention, theinvention also resides in the claims hereinafter appended.

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TABLE 1 SNPs from genes of endocannabinoid systems and response tocannabinoids Nucleotide Target Conditions Function Category Gene SNPnumber Change Reference(s) Cannabis Response Receptor Receptor CNR1rs806380 c.−63−9597 T > C Ref. #24 Cannabis Response Receptor ReceptorCNR1 rs806368 c.*3475 A > G Ref. #24 Cannabis Response Receptor ReceptorCNR1 rs1049353 c.1359 A > G Ref. #24 Cannabis Response Receptor ReceptorCNR1 rs2180619 Refs. #46 and #23 Cannabis Response Receptor ReceptorCNR1 rs2023239 Refs. #47 and #27 Cannabis Response Receptor ReceptorCNR2 rs2501432/rs35761398 Refs. #24, #38, (Same locus) #42, and #45Cannabis Response Receptor Receptor CNR2 rs2229579 His316Tyr Ref. #24Cannabis Response Transport Transporters ABCB1 rs1045642 3435C > T Ref.#24 Cannabis Response Biotransformation Enzyme FAAH rs34420 385C > ARef. #24 Cannabis Response Biotransformation Enzyme COMT rs4680 472A > GRef. #24 Cannabis Response Others Receptor GABRA2 rs279858 231A > G Ref.#1 Cannabis Response Others Receptor GABRA2 rs279871 Ref. #1 CannabisResponse Others Receptor GABRA2 rs279826 Ref. #1 Cannabis ResponseOthers Signaling NRG1 rs17664708 122−16329C > T Ref. #19 CannabisResponse Enzymes Enzyme CYP1A2 rs762551 Ref. #21 Cannabis ResponseEnzymes Enzyme CYP2C9 rs1057910 Ref. #24 Cannabis Response EnzymesEnzyme CYP2C19 rs4244285 Ref. #24 Cannabis Response Enzymes EnzymeCYP3A4 rs67666821 Ref. #24 Cannabis Response Enzymes Enzyme CYP3A4rs4646438 Ref. #24 Cannabis Response Signaling Signaling MAPK14rs12199654 Ref. #24 Cannabis Response Signaling Signaling NRG1rs17664708 Ref. #24

TABLE 2 SNPs associated responses of pain treatment Nucleotide TargetConditions Functions Category Gene SNP number Change Reference(s) Painmedicine Receptors Receptor TRPV1 rs222747 Ref. #7 Pain medicineReceptors Receptor TRPV1 rs8065080 Ref. #14 Pain medicine ReceptorsTransporters FABP1 rs2241883 Ref. #39 Pain medicine Receptors ReceptorOPRM1 rs1799971 A118G Ref. #37 Pain medicine Transport TransportersABCB1 rs1045642 3435C > T Ref. #29 Pain medicine BiotransformationEnzyme COMT rs4680 472A > G Ref. #37 Pain medicine Metabolism EnzymeCYP2D6 rs16947 CYP2D6*1/*2 Ref. #29 Pain medicine Metabolism EnzymeCYP2D6 rs1135840 CYP2D6*1/*2 Ref. #29 Pain medicine Metabolism EnzymeCYP2D6 rs35742686 CYP2D6*3/*3 Ref. #29 Pain medicine Metabolism EnzymeCYP2B6 rs35303484 CYP2B6*11; Ref. #48 c136A > G; M46V Pain medicineMetabolism Enzyme CYP2C9 rs1057910 CYP2C9*3/*3 Ref. #29 Pain medicineImmune Hypersensitivity Signaling HLA rs3909184 HLA-B*1502 Ref. #29 Painmedicine Immune Hypersensitivity Signaling HLA rs2844682 HLA-B*1502 Ref.#29 Pain medicine Immune Hypersensitivity Signaling HLA rs1061235HLA-A*3101 Ref. #29 Pain medicine Immune Hypersensitivity Signaling HLArs2734331 HLA-B*3801 Ref. #29 Pain medicine Immune HypersensitivitySignaling HLA (Q126H) HLA-DBQ1 (126Q) Ref. #29 Pain medicine ImmuneHypersensitivity Signaling HLA A158T KLA-B(158T) Ref. #29

TABLE 3 SNPs associated with anxiety/depression and responses oftreatment Target Conditions Functions Category Gene SNP numberReference(s) Depression/anxiety Endocannabinoids Receptor CNR1 rs2180619Refs. #46, #23, and #30 Depression/anxiety Endocannabinoids ReceptorCNR1 rs1049353 Ref. #45 Depression/anxiety Endocannabinoids ReceptorCNR1 rs806368 Ref. #45 Depression/anxiety Endocannabinoids Receptor CNR1rs806371 Ref. #45 Depression/anxiety Endocannabinoids Receptor CNR1rs2023239 Ref. #45 Depression/anxiety Endocannabinoids Receptor CNR1rs806379 Ref. #45 Depression/anxiety Endocannabinoids Receptor CNR1rs1535255 Ref. #45 Depression/anxiety Endocannabinoids Receptor CNR1rs806369 Ref. #45 Depression/anxiety Endocannabinoids Receptor CNR1rs4707436 Ref. #45 Depression/anxiety Endocannabinoids Receptor CNR1rs12720071 Ref. #45 Depression/anxiety Endocannabinoids Receptor CNR1rs806366 Ref. #45 Depression/anxiety Endocannabinoids Receptor CNR1rs7766029 Ref. #45 Depression/anxiety Endocannabinoids Receptor CNR2rs250143l Ref. #45 Depression/anxiety Endocannabinoids Enzyme FAAHrs2295633 Refs. #49 and #45 Depression/anxiety Endocannabinoids EnzymeFAAH rs324420 Refs. #33 and #45 Depression/anxiety EndocannabinoidsSignaling AKT1 rs1130233 Ref. #5 Depression/anxiety Autoimmune SignalingIL-1β rs16944 Ref. #45 Depression/anxiety Autoimmune Signaling IL-1βrs1143627 Ref. #45 Depression/anxiety Autoimmune Signaling IL-1βrs1143633 Ref. #45 Depression/anxiety Autoimmune Signaling IL-1βrs1143643 Ref. #45 Depression/anxiety Autoimmune Enzyme COX-2 rs4648308Ref. #45 Depression/anxiety Autoimmune Enzyme COX-2 rs20417 Ref. #45Depression/anxiety HPA Axis Receptor NR3C1 rs6189 Ref. #45Depression/anxiety HPA Axis Receptor NR3C1 rs6190 Ref. #45Depression/anxiety HPA Axis Receptor NR3C1 rs41423247 Ref. #45Depression/anxiety HPA Axis Receptor NR3C1 rs1876828 Ref. #13Depression/anxiety HPA Axis Receptor NR3C1 rs242939 Ref. #13Depression/anxiety HPA Axis Receptor NR3C1 rs242941 Ref. #13Depression/anxiety HPA Axis Receptor NR3C1 rs6198 Ref. #45Depression/anxiety HPA Axis Enzyme FKBP5 rs4713916 Ref. #45Depression/anxiety HPA Axis Enzyme FKBP5 rs1360780 Ref. #45Depression/anxiety Glutamatergic System Signaling GRIK4 rs12800734 Ref.#50 Depression/anxiety Glutamatergic System Signaling GRIK4 rs1954787Ref. #50 Depression/anxiety Serotoninergic System Receptor HTR2Ars17288723 Ref. #50 Depression/anxiety Serotoninergic SystemTransporters SLC6A4 5HTTLPR Refs. #13 and #51 Depression/anxietySerotoninergic System Transporters SLC6A4 STin2 VNTR Ref. #13Depression/anxiety Serotoninergic System Receptor HTR1A rs6295 Refs. #13and #3 Depression/anxiety Serotoninergic System Receptor HTR1B rs62898Ref. #13 Depression/anxiety Serotoninergic System Receptor HTR2A rs6311Ref. #13 Depression/anxiety Serotoninergic System Receptor HTR2Ars7997012 Ref. #13 Depression/anxiety Serotoninergic System ReceptorHTR2A rs1928040 Ref. #13 Depression/anxiety Serotoninergic System EnzymeTPH1 rs1800532 Ref. #13 Depression/anxiety Serotoninergic System EnzymeTPH2 rs120074175 Ref. #13 Depression/anxiety Noradrenergic System EnzymeCOMT rs4680 Ref. #13 Depression/anxiety Noradrenergic System Enzyme MAOAVNTR 1.2 kb Ref. #13 upstream coding sequence Depression/anxietyNoradrenergic System Transporters SLC6A2 rs5569 Ref. #13Depression/anxiety Dopaminergic System Transporters SLC6A3 3′UTR 40-bpVNTR Ref. #13 Depression/anxiety Signaling and Growth Signaling BDNFrs6265 Ref. #13 Factors Depression/anxiety Signaling and GrowthSignaling GNB3 rs5443 Ref. #13 Factors Depression/anxiety Enzymes EnzymeACE Insertion or deletion Ref. #13 Depression/anxiety Enzymes EnzymeGSK3B rs334558 Ref. #13 Depression/anxiety Pharmacokinetics TransportersABCB1 rs2032582 Refs. #13 and #43 Depression/anxiety PharmacokineticsTransporters ABCB1 rs1045642 Ref. #26

TABLE 4 SNPs associated insomnia and responses of treatment TargetConditions Functions Category Gene SNP number Reference(s) SleepDisorder Endocannabinoids Receptor CNR1 rs78783387 Ref. #26 SleepDisorder Endocannabinoids Enzyme FAAH rs324420 Refs. #33, #45 SleepDisorder Enzymes Enzyme CYP2D6 Gene Copy Nos. Ref. #21 Sleep DisorderEnzymes Enzyme CYP2C19 Various Alleles Ref. #21 Sleep Disorder EnzymesEnzyme CYP3A4 Various Alleles Ref. #21 Sleep Disorder SerotoninergicSystem Receptor HTR2A rs6311 Ref. #21 Sleep Disorder Enzymes EnzymeCYP1A2 rs762551 Ref. #21 Sleep Disorder Melatoninergic System ReceptorMTNR1d rs2119882 Ref. #21 Sleep Disorder Organic Cation TransportersSLC22A4 rs195152 Ref. #21 Sleep Disorder Serotoninergic System ReceptorHTR1B rs130060 Ref. #21 Sleep Disorder Serotoninergic System ReceptorHTR2A rs6313 Ref. #21 GWAS/Insomnia NA SCFD2 rs574753165 Ref. #18GWAS/Insomnia NA WDR27 rs13192566 Ref. #18 GWAS/Insomnia NA MEIS1rs113851554 Ref. #18 GWAS/Insomnia NA WDR27 rs71554396 Ref. #18GWAS/Insomnia NA CEP152 rs2725544 Ref. #18

TABLE 5 Primers designed for selected SNPs for testing Chromo- someGenes SNPs Notes Position Forward Primer Reverse Primer OPRM1 rs1799971NC_000006.12:g.154039662 154360797 AAAAGTCTCGGTGCTCC CTGGCGCTTTCCTTACA > G TGG - SEQ ID NO: 1 CTGA - SEQ ID NO: 2 TRPV1 rs222747NC_000017.11:g.3589906   3493200 CTAAGGGGAGGTTTGGG AGCCCTACAGGCTGGTC > A CAG - SEQ ID NO: 3 ATGA - SEQ ID NO: 4 TRPV1 rs8065080NC_000017.11:g.3577153   3480447 GTCATGTGAGATGGGGC CAGTGTGTCCTCTGTCT > C CAA - SEQ ID NO: 5 CACC - SEQ ID NO: 6 HTR2A rs6311NC_000013.11:g.46897343  47471478 AGGTACAGACTTGGCCA GGCCTTTTGTGCAGATC > T CAA - SEQ ID NO: 7 TCCC - SEQ ID NO: 8 HTR2A rs6313NC_000013.11:g.46895805  47469940 GCATGTACACCAGCCTC GTGGCATGCACATGCTG > A AGT - SEQ ID NO: 9 CTTT - SEQ ID NO: 10 ABCB1 rs1045642NC_000007.14:g.87509329  87138645 TGAATGTTCAGTGGCTC ACAGGAAGTGTGGCCA > G CGA - SEQ ID NO: 11 AGATG - SEQ ID NO: 12 ABCB1 rs2032582NC_000007.14:g.87531302  87160618 GCAGGCTATAGGTTCCA AGTCCAAGAACTGGCTA > C GGC - SEQ ID NO: 13 TTGCT - SEQ ID NO: 14 CNR1 rs1049353NC_000006.12:g.88143916  88853635 CCGGAGCATGTTTCCCT GTAGCCAAAGGTTTCCC > T CTT - SEQ ID NO: 15 CTCCT - SEQ ID NO: 16 CNR1 rs2180619NC_000006.12:g.88168233  88877952 ACCAGGGTGTGTCAGTG TGGGGAAGGCTCTACTG > A TTG - SEQ ID NO: 17 CACA - SEQ ID NO: 18 CNR1 rs806368NC_000006.12:g.88140381  88850100 GCCCAACCACCAGATGA TGCAACGATGTTACCAT > C GAA - SEQ ID NO: 19 GCTCA - SEQ ID NO: 20 CNR1 rs806380NC_900006.12:g.88154934  88864653 TCACTGTTGCTATGGAC GTGCCTTGGCACTTTTA > G TCCT - SEQ ID NO: 21 CTTGA - SEQ ID NO: 22 CNR2 rs2229579NC_000001.11:g.23874672  24201162 GGCTGTGCTCCTCATCT GGGTCCGTGTCTAGGTG > A GTT - SEQ ID NO: 23 G - SEQ ID NO: 24 CNR2 rs35761398NC_000001.11:g.23875429_  24201919 AGGTGAGGTCATTCTTG AGTCACGCTGCCAATC23875430delTTinsCC TGCT - SEQ ID NO: 25 TTCA - SEQ ID NO: 26 COMT rs4680NC_000022.11:g,19963748  19951271 CTGCTCTTTGGGAGAGG CCACCTTGGCAGTTTAG > A TGG - SEQ ID NO: 27 CCCA - SEQ ID NO: 28 CYP2C19 rs4244285NC_000010.11:g.94781859  96541616 TGTGCAAACTCTTTTAA CACAAATACGCAAGCG > A CCTATGCT - SEQ ID  AGTCACA - SEQ ID NO: NO: 29 30 CYP2C9 rs1057910NC_000010.11:g.94981296  96741053 ACCCCTGAATTGCTACA ACCCGGTGATGGTAGA > C ACA - SEQ ID NO: 31 AGGTT - SEQ ID NO: 32 CYP2C9 rs1799853NC_000010.11:g.94942290  96702047 GCAGTGAAGGAAGCCC CCCTTGGCTCTCAGCTC > T TGAT - SEQ ID NO: 33 TCAA - SEQ ID NO: 34 CYP3A4 rs55785340NC_000007.14:g.99768360  99365983 GTCTTTGGGGCCTACAG AAGTGGATGAATTACA > G CAT - SEQ ID NO: 35 ATGGTGA - SEQ ID NO: 36 CYP3A4 rs67784355NC_000007.14:g.99762206  99359829 GGATTTCAGTCCCTGGG GGGCCTTGTACCTTTCG > A GTG - SEQ ID NO: 37 AGGG - SEQ ID NO: 38 CYP3A4 rs12721629NC_000007.14:g.99762177  99359800 GGATTTCAGTCCCTGGG GGGCCTTGTACCTTTCG > A GTG - SEQ ID NO: 39 AGGG - SEQ ID NO: 40 CYP3A4 rs4987161NC_000007.14:g.99768458  99366081 GAAGAGGAATCGGCTCT TGAGAGAAAGAATGGA > G GGG - SEQ ID NO: 41 ATCCAAAA - SEQ ID NO: 42 FAAH rs324420NC_000001.11:g.46405089  46870761 TCCCTAGTGAGGCAGAT TGACCCAAGATGCAGC > A GCT - SEQ ID NO: 43 AGCAG - SEQ ID NO: 44 FAAH rs2295633NC_000001.11:g.46408711  46874383 ACTGCAGGGTCCTGGAA AACCCTGCCCACAAGA > G GTA - SEQ ID NO: 45 ATAGC - SEQ ID NO: 46 MGLL rs604300NC_000003.12:g.127724009 127442852 GAAGGAAAGGGGAGTT CTAACCCCCAGGATCTA > G GGGG - SEQ ID NO: 47 CGGA - SEQ ID NO: 48 GABRA2 rs279826NC_000004.12:g.46332192  46334209 CACATAATGGGGAGTG ACCAGTTCCATAGAATA > G GGGG - SEQ ID NO: 49 CCAAGAGT - SEQ ID NO: 50 GABRA2 rs279858NC_000004.12:g.46312576  46314593 TGGAGCAGTTTGACTGA ACAGCTAGATTGGCTGT > C GACC - SEQ ID NO: 51 GTTGT - SEQ ID NO: 52 GABRA2 rs279871NC_000004.12:g.46303716  46305733 CAATATCATGGGACGTG AAAACAATACTCCCCGT > C   AGCTG - SEQ ID NO: CCCC - SEQ ID NO: 54 53 MAPK14 rs12199654NC_000006.12:g.36041718  36009495 ACTTCCGTTGGAATGGG ACTGGGTTCACCCTACA > G ATTCA - SEQ ID NO: CTGA - SEQ ID NO: 56 55 NRG1 rs17664708NC_000008.11:g.32579499  32437017 CAGCACTGGGAGGTGAT TGTCATGTTGTTGGCTC > T CTG - SEQ ID NO: 57 TGGA - SEQ ID NO: 58 AKT1 rs1130233NC_000014.9:g.104773557 105239894 GGGTGACTTGTTCCTGC GCACAGAGAGGACACC > T TGA - SEQ ID NO: 59 AGCAT - SEQ ID NO: 60 CNR2 rs2501431NC_000001.11:g.23875153  24201643 TCTGATCCTGTCCTCCC TCTTGGCCAACCTCACG > A ACC - SEQ ID NO: 61 ATCC - SEQ ID NO: 62 HTR1A rs6295NC_000005.10:g.63962738  63258565 GAGGTTTGCAGGCTCTG GTGTCAGCATCCCAGAC > G GTA - SEQ ID NO: 63 GTGG - SEQ ID NO: 64 HTR2A rs7997012NC_000013.11:g.46837850  47411985 CTTGGAGGCACAGCTCA ACTGCCTCACTCTTGCA > G TCA - SEQ ID NO: 65 CATC - SEQ ID NO: 66 CNR1 rs806371NC_000006.12:g.88146644  88856363 GATTGTCTCTCCCCCAA AGCAGGTTGGTGACAT > G CCC - SEQ ID NO: 67 CAAGT - SEQ ID NO: 68 CNR1 rs12720071NC_000006.12:g.88141462  88851181 TTGCCAGTCTTTTGTCCT AATGCATGGTCAGGGT > C GC - SEQ ID NO: 69 CAAGT - SEQ ID NO: 70 CNR1 rs1406977NC_000006.11:g.8884821  88884821 GCACACTTGTGTCACCA ATGTGGGGAGAGATG C > TACC - SEQ ID NO: 71 CTCCT - SEQ ID NO: 72 PTGS2 rs20417NC_000001.11:g.186681189 186650321 CCTGCAAATTCTGGCCA CACTTGGCTTCCTCTCC > G TCG - SEQ ID NO: 73 GAGG - SEQ ID NO: 74 SLC6A4 5-HTTLPR AC104984   26096 ATGCCAGCACCTAACCC GGACCGCAAGGTGGG CTAATGT - SEQ ID NO:CGGGA - SEQ ID NO: 76 75

TABLE 6A NGS data report of SNPs SNP Index db_xref Gene Chrom PositionCoverage Trans Accession 1 rs2229579 CNR2 1 24201162 3004 NM_001841.2 2rs2501431 CNR2 1 24201643 0 NM_001841.2 3 rs35761398 CNR2 1 242019193305 NM_001841.2 4 rs2501432 CNR2 1 24201920 3275 NM_001841.2 5 rs324420FAAH 1 46870761 4096 NM_001441.2 6 rs2295633 FAAH 1 46874383 2303NM_001441.2 7 rs20417 PTGS2 1 186650321 2102 8 rs604300 MGLL 3 1274428528670 NM_007283.5 9 rs279871 GABRA2 4 46305733 3473 NM_000807.2 10rs279858 GABRA2 4 46314593 470 NM_000807.2 11 rs279826 GABRA2 4 463342091021 NM_000807.2 12 rs6295 HTR1A 5 63258565 998 13 rs12199654 MAPK14 636009495 1203 NM_001315.2 14 rs806368 CNR1 6 88850100 348 NM_001160226.115 rs12720071 CNR1 6 88851181 1334 NM_001160226.1 16 rs1049353 CNR1 688853635 4142 NM_001160226.1 17 rs806371 CNR1 6 88856363 9379NM_001160226.1 18 rs806380 CNR1 6 88864653 1116 NM_001160226.1 19rs2180619 CNR1 6 88877952 2302 20 rs1406977 CNR1 6 88884821 0 21rs1799971 OPRM1 6 154360797 4218 NM_001145279.1 22 rs1045642 ABCB1 787138645 11263 NM_000927.4 23 rs2032582 ABCB1 7 87160618 10755NM_000927.4 24 rs12721629 CYP3A4 7 99359800 4954 NM_017460.5 25rs67784355 CYP3A4 7 99359829 4756 NM_017460.5 26 rs55785340 CYP3A4 799365983 6977 NM_017460.5 27 rs4987161 CYP3A4 7 99366081 6667NM_017460.5 28 rs17664708 NRG1 8 32437017 1277 NM_013956.3 29 rs4244285CYP2C19 10 96541616 737 NM_000769.1 30 rs28371674 CYP2C9 10 967020471002 NM_000771.3 31 rs1057910 CYP2C9 10 96741053 3383 NM_000771.3 32rs79970l2 HTR2A 13 47411985 5884 NM_000621.3 33 rs6313 HTR2A 13 474699401982 NM_000621.3 34 rs6311 HTR2A 13 47471478 1193 35 rs1130233 AKT1 14105239894 2057 NM_001014431.1 36 rs8065080 TRPV1 17 3480447 1624NM_018727.5 37 rs222747 TRPV1 17 3493200 1 NM_018727.5 38 rs4680 COMT 2219951271 1537 NM_000754.3

TABLE 6B NGS data report of SNPs Mutation Call: Index ReferenceAlternative A % C % G % T % Relative To CDS CDS 1 G A 0.23 0 99.73 0.031 2 G — 0 0 0 0 1 3 T C 0.15 53.92 0.33 45.6 c.189A > AG 1 4 T C 0.1253.25 0.06 46.56 c.188A > AG 1 5 C K 48.19 51.27 0.27 0.27 c.385C > AC 36 A G 1.22 0 98.74 0 c.1077+127A > G 7 C T 0.05 99.67 0 0.29 8 A G 0.140 99.86 0 c.263−1443T > C 9 T C 0.03 99.91 0 0.06 c.704−104A > G 10 T C0 100 0 0 c.396A > G 4 11 A G 0.1 0 99.8 0.1 c.255+423T > C 12 C G 0.148.5 51.3 0.1 c.−1019C > CG 13 A G 99.42 0.17 0.42 0 14 T C 0 47.99 052.01 c.*3475A > AG 15 T C 0.22 52.4 0.22 47.15 c.*2394A > AG 16 C T0.05 99.59 0 0.36 1 17 T C 0.04 0.33 0.03 99.59 18 A G 0 0 100 0c.−206−7128T > C 19 G A 99 0.35 0.52 0.13 c.−452−2185G > A 20 C — 0 0 00 21 A G 99.36 0.05 0.55 0.05 2 22 A G 99.15 0.18 0.56 0.1 25 23 A G99.38 0.07 0.45 0.1 20 24 G T 0.16 0 99.64 0.2 11 25 G A 0.17 0.02 99.810 11 26 A G 99.64 0.04 0.3 0.01 7 27 A G 99.46 0.04 0.31 0.18 7 28 C A0.08 99.84 0 0.08 29 G A 0.14 0 99.73 0.14 5 30 C T 0 99.6 0.1 0.3 3 31A G 99.29 0.03 0.62 0.06 7 32 A G 0.05 0 99.9 0.05 c.614−2211T > C 33 GA 48.69 0 51.16 0.15 c.102C > CT 1 34 C T 0 49.12 0 50.88 c.−689−309C >CT 35 C T 0.05 48.71 0.05 51.14 c.726G > AG 8 36 T C 0 1.05 0.12 98.8311 37 C — 0 100 0 0 5 38 G A 48.8 0 51.2 0 c.472G > AG 2 Zygosity:Heterozygous: Index #s 1-5, 7, 12-17, 20-31, and 33-38 Homozygous: Index#s 6, 8-11, 18, 19, and 32

TABLE 7 Weighting Values for Dosage Impacts of SNP Genotypes DragCannabis CBD THC Dependence Gene Gene Group SNP Allele Dosage DosageDosage THC) OPRM1 Transporter/Receptor rs1799971 - Refs. 37 and 11 A/A 11 1 1 OPRM1 Transporter/Receptor rs1799971 - Ref. 37 A/G 1 1 1 1 OPRM1Transporter/Receptor rs1799971 - Ref. 37 G/G 1 1 1 1 TRPV1Transporter/Receptor rs222747 - Refs. 6 and 7 C/C 1 1 1 1 TRPV1Transporter/Receptor rs222747 - Refs. 6 and 7 C/G 1 1 1 1 TRPV1Transporter/Receptor rs222747- Refs. 6 and 7 G/G 1 1 1 1 TRPV1Transporter/Receptor rs8065080 - Refs. 6 and 14 T/T 1 1 1 1 TRPV1Transporter/Receptor rs8065080 - Refs. 6 and 14 T/C 1 1 1 1 TRPV1Transporter/Receptor rs8065080 - Refs. 6 and 14 C/C 1 0.5 1 1 HTR2ATransporter/Receptor rs6311 - Refs. 13 and 21 C/C 1 1 1 1 HTR2ATransporter/Receptor rs6311 - Refs. 13 and 21 C/T 1 1 1.5 1 HTR2ATransporter/Receptor rs6311 - Refs. 13 and 21 T/T 1 1 1.5 1 HTR2ATransporter/Receptor rs6313 - Refs. 21 and 12 G/G 1 1 1 1 HTR2ATransporter/Receptor rs6313 - Refs. 21 and 12 G/A 1 1 1 1 HTR2ATransporter/Receptor rs6313 - Refs. 21 and 12 A/A 1 1 0.64 1 ABCB1Transporter/Receptor rs1045642 - Refs. 17, 26, and 4 A/A 1 1 1 1 ABCB1Transporter/Receptor rs1045642 - Refs. 17, 26, and 4 A/G 1 1 1 1 ABCB1Transporter/Receptor rs1045642 - Refs. 17, 26, and 4 G/G 1 1 1 0.5 ABCB1Transporter/Receptor rs2032582 - Refs. 13 and 43 A/A 1 1 1 1 ABCB1Transporter/Receptor rs2032582 - Refs. 13 and 43 A/C 1 1 1 1 ABCB1Transporter/Receptor rs2032582 - Refs. 13 and 43 C/C 1 1 1 1 CNR1Transporter/Receptor rs1049353 - Refs. 24, 45, and 35 C/C 1.25 1 1 1CNR1 Transporter/Receptor rs1049353 - Refs. 24, 45, and 35 C/T 1 1 1 1CNR1 Transporter/Receptor rs1049353 - Refs. 24, 45, and 35 T/T 0.75 1 11 CNR1 Transporter/Receptor rs2180619 - Refs. 46, 30, and 23 G/G 1 1 10.5 CNR1 Transporter/Receptor rs2180619 - Refs. 46, 30, and 23 G/A 1 1 11 CNR1 Transporter/Receptor rs2180619 - Refs. 46, 30, and 23 A/A 1 1 1 1CNR1 Transporter/Receptor rs806368 - Ref. 35 T/T 1.5 1 1 1 CNR1Transporter/Receptor rs806368 - Ref. 35 T/C 1 1 1 1 CNR1Transporter/Receptor rs806368 - Ref. 35 C/C 1 1 1 1 CNR1Transporter/Receptor rs806371 - Refs. 45 and 35 T/T 1 1 1 1 CNR1Transporter/Receptor rs806371 - Refs. 45 and 35 T/G 1 1 1 1 CNR1Transporter/Receptor rs806371 - Refs. 45 and 35 G/G 1 1 1 1 CNR1Transporter/Receptor rs806368-rs806371 - Ref. 45 T/T/T/T 1.5 1 1 1 CNR1Transporter/Receptor rs806368-rs806371 - Ref. 45 Other 1 1 1 1 CNR1Transporter/Receptor rs806380 - Ref. 22 A/A 1 1 1 0.75 CNR1Transporter/Receptor rs806380 - Ref. 22 A/G 1 1 1 1 CNR1Transporter/Receptor rs806380 - Ref. 22 G/G 1 1 1 1 CNR1Transporter/Receptor rs12720071 - Ref. 20 T/T 1 1 1 1 CNR1Transporter/Receptor rs12720071 - Ref. 20 T/C 1 1 1 1 CNR1Transporter/Receptor rs12720071 - Ref. 20 C/C 1 1 1 1 CNR2Transporter/Receptor rs2229579 - Refs. 44 and 9 G/G 1 1 1 1 CNR2Transporter/Receptor rs2229579 - Refs. 44 and 9 G/A 1 1 1 1 CNR2Transporter/Receptor rs2229579 - Refs. 44 and 9 A/A 1 1 1 1 CNR2Transporter/Receptor rs35761398 - Refs. 25 and 9 T/T 1 1 1 1 CNR2Transporter/Receptor rs35761398 - Refs. 25 and 9 T/C 1 1 1 1 CNR2Transporter/Receptor rs35761398 - Refs. 25 and 9 C/C 1.5 1 1 1 CNR2Transporter/Receptor rs2501432 - Refs. 25 and 9 T/T 1 1 1 1 CNR2Transporter/Receptor rs2501432 - Refs. 25 and 9 T/C 1 1 1 1 CNR2Transporter/Receptor rs2501432 - Refs. 25 and 9 C/C 1.5 1 1 1 COMTMetabolic Enzyme rs4680 - Ref. 24 G/G 1 1 1 0.75 COMT Metabolic Enzymers4680 - Ref. 24 G/A 1 1 1 1 COMT Metabolic Enzyme rs4680 - Ref. 24 A/A1 1 1 1 CYP2C19 Metabolic Enzyme rs4244285 - Refs. 15 and 41 G/G 1 1 1 1CYP2C19 Metabolic Enzyme rs4244285 - Refs. 15 and 41 G/A 1 0.75 1 1CYP2C19 Metabolic Enzyme rs4244285 - Refs. 15 and 41 A/A 1 0.5 1 1CYP2C9 Metabolic Enzyme rs1057910 - Refs. 29 and 41 A/A 1 1 1 1 CYP2C9Metabolic Enzyme rs1057910 - Refs. 29 and 41 A/C 1 1 0.65 1 CYP2C9Metabolic Enzyme rs1057910 - Refs. 29 and 41 C/C 1 1 0.3 1 CYP2C9Metabolic Enzyme rs28371674 - Refs. 29 and 41 C/C 1 1 1 1 CYP2C9Metabolic Enzyme rs28371674 - Refs. 29 and 41 C/T 1 1 0.8 1 CYP2C9Metabolic Enzyme rs28371674 - Refs. 29 and 41 T/T 1 1 0.6 1 CYP3A4Metabolic Enzyme rs55785340 - Refs. 41 A/A 1 1 1 1 CYP3A4 MetabolicEnzyme rs55785340 - Refs. 41 A/G 0.75 1 1 1 CYP3A4 Metabolic Enzymers55785340 - Refs. 41 G/G 0.5 1 1 1 CYP3A4 Metabolic Enzyme rs67784355 -Refs. 41 G/G 1 1 1 1 CYP3A4 Metabolic Enzyme rs67784355 - Refs. 41 G/A0.75 1 1 1 CYP3A4 Metabolic Enzyme rs67784355 - Refs. 41 A/A 0.5 1 1 1CYP3A4 Metabolic Enzyme rs12721629 - Refs. 41 G/G 1 1 1 1 CYP3A4Metabolic Enzyme rs12721629 - Refs. 41 G/A 0.75 1 1 1 CYP3A4 MetabolicEnzyme rs12721629 - Refs. 41 A/A 0.5 1 1 1 CYP3A4 Metabolic Enzymers4987161 - Refs. 41 A/A 1 1 1 1 CYP3A4 Metabolic Enzyme rs4987161 -Refs. 41 A/G 0.75 1 1 1 CYP3A4 Metabolic Enzyme rs4987161 - Refs. 41 G/G0.5 1 1 1 FAAH Metabolic Enzyme rs324420 - Refs. 33 and 40 C/C 1 1 1 1FAAH Metabolic Enzyme rs324420 - Refs. 33 and 40 C/A 1 0.75 1 0.75 FAAHMetabolic Enzyme rs324420 - Refs. 33 and 40 A/A 1 0.5 1 0.5 FAAHMetabolic Enzyme rs2295633 - Refs. 28 and 32 A/A 1 1 1 1 FAAH MetabolicEnzyme rs2295633 - Refs. 28 and 32 A/G 1 1 1 1 FAAH Metabolic Enzymers2295633 - Refs. 28 and 32 G/G 1 1 1 1 MGLL Metabolic Enzyme rs604300 -Ref. 8 A/A 1 1 1 1 MGLL Metabolic Enzyme rs604300 - Ref. 8 A/G 1 1 1 1MGLL Metabolic Enzyme rs604300 - Ref. 8 G/G 1 1 1 0.5 GABRA2Transporter/Receptor rs279826 - Ref. 1 A/A 1 1 1 1 GABRA2Transporter/Receptor rs279826 - Ref. 1 A/G 1 1 1 1 GABRA2Transporter/Receptor rs279826 - Ref. 1 G/G 1 1 1 1 GABRA2Transporter/Receptor rs279858 - Ref. 1 T/T 1 1 1 1 GABRA2Transporter/Receptor rs279858 - Ref. 1 T/C 1 1 1 1 GABRA2Transporter/Receptor rs279858 - Ref. 1 C/C 1 1 1 1 GABRA2Transporter/Receptor rs279871 - Ref. 1 T/T 1 1 1 1 GABRA2Transporter/Receptor rs279871 - Ref. 1 T/C 1 1 1 1 GABRA2Transporter/Receptor rs279871 - Ref. 1 C/C 1 1 1 1 GABRA2Transporter/Receptor rs279826-rs279858-rs279871 - A/T/T 1 1 1 0.5 Ref. 1GABRA2 Transporter/Receptor rs279826-rs279858-rs279871 - G/C/C 1 1 10.75 Ref. 1 GABRA2 Transporter/Receptor rs279826-rs279858-rs279871 -Other 1 1 1 1 Ref. 1 MAPK14 Signaling rs12199654 - Ref. 36 A/A 1 1 1 1MAPK14 Signaling rs12199654 - Ref. 36 A/G 1 1 1 1 MAPK14 Signalingrs12199654 - Ref. 36 G/G 1 1 1 1 MAPK14/ Signalingrs12199654-rs12720071 - Ref. A/A/T/C 1 1 1 0.5 CNR1 36 MAPK14/ Signalingrs12199654-rs12720071 - Ref. A/A/C/C 1 1 1 0.5 CNR1 36 NRG1 Signalingrs17664708 - Ref. 19 C/C 1 1 1 1 NRG1 Signaling rs17664708 - Ref. 19 C/T1 1 1 0.75 NRG1 Signaling rs17664708 - Ref. 19 T/T 1 1 1 0.5 AKT1Signaling rs1130233 - Ref. 5 C/C 1 1 1 1 AKT1 Signaling rs1130233 - Ref.5 C/T 1 1 0.5 1 AKT1 Signaling rs1130233 - Ref. 5 T/T 1 1 0.5 1 CNR2Transporter/Receptor rs2501431 - Ref. 24 1 1 1 1 CNR2Transporter/Receptor rs2501431 - Ref. 24 1 1 1 1 CNR2Transporter/Receptor rs2501431 - Ref. 24 1 1 1 1 HTR1ATransporter/Receptor rs6295 - Refs. 2 and 3 C/C 1 1 1 1 HTR1ATransporter/Receptor rs6295 - Refs. 2 and 3 C/G 1.5 1 1 1 HTR1ATransporter/Receptor rs6295 - Refs. 2 and 3 G/G 1.5 1 1 1 HTR2ATransporter/Receptor rs7997012 - Ref. 34 A/A 1 1 1 1 HTR2ATransporter/Receptor rs7997012 - Ref. 34 A/G 1 1 1 1 HTR2ATransporter/Receptor rs7997012 - Ref. 34 G/G 1 1 1.22 1 CNR1Transporter/Receptor rs1406977 - Ref. 24 1 1 1 1 CNR1Transporter/Receptor rs1406977 - Ref. 24 1 1 1 1 CNR1Transporter/Receptor rs1406977 - Ref. 24 1 1 1 1 PTGS2 Metabolic Enzymers20417 - Refs. 16, 10, and 24 C/C 1 1 1 1 PTGS2 Metabolic Enzymers20417 - Refs. 16, 10, and 24 C/G 1 1 1 1 PTGS2 Metabolic Enzymers20417 - Refs. 16, 10, and 24 G/G 1 1 1 1 SLC6A4 Transporter/Receptor5-HTTLPR - Ref. 24 1 1 1 1 SLC6A4 Transporter/Receptor 5-HTTLPR - Ref.24 1 1 1 1 SLC6A4 Transporter/Receptor 5-HTTLPR - Ref. 24 1 1 1 1

TABLE 8 Weighting Values for Genotypes of a Test Example Drug CannabisCBD THC Dependence Dosage Dosage Dosage (THC) Gene Gene Group SNP Allele(a_(i)) (b_(i)) (c_(i)) (d_(i)) OPRM1 Transporter/Receptor rs1799971 A/A1 1 1 1 TRPV1 Transporter/Receptor rs8065080 T/T 1 1 1 1 HTR2ATransporter/Receptor rs6311 C/T 1 1 1.5 1 HTR2A Transporter/Receptorrs6313 G/A 1 1 1 1 ABCB1 Transporter/Receptor rs1045642 A/A 1 1 1 1ABCB1 Transporter/Receptor rs2032582 A/A 1 1 1 1 CNR1Transporter/Receptor rs1049353 C/C 1.25 1 1 1 CNR1 Transporter/Receptorrs2180619 A/A 1 1 1 1 CNR1 Transporter/Receptor rs806368 T/C 1 1 1 1CNR1 Transporter/Receptor rs806371 T/T 1 1 1 1 CNR1 Transporter/Receptorrs806380 G/G 1 1 1 1 CNR1 Transporter/Receptor rs12720071 T/C 1 1 1 1CNR2 Transporter/Receptor rs2229579 G/G 1 1 1 1 CNR2Transporter/Receptor rs35761398 T/C 1 1 1 1 CNR2 Transporter/Receptorrs2501432 T/C 1 1 1 1 COMT Metabolic Enzyme rs4680 G/A 1 1 1 1 CYP2C19Metabolic Enzyme rs4244285 G/G 1 1 1 1 CYP2C9 Metabolic Enzyme rs1057910A/A 1 1 1 1 CYP2C9 Metabolic Enzyme rs28371674 C/C 1 1 1 1 CYP3A4Metabolic Enzyme rs55785340 A/A 1 1 1 1 CYP3A4 Metabolic Enzymers67784355 G/G 1 1 1 1 CYP3A4 Metabolic Enzyme rs12721629 G/G 1 1 1 1CYP3A4 Metabolic Enzyme rs4987161 A/A 1 1 1 1 FAAH Metabolic Enzymers324420 C/A 1 0.75 1 0.75 FAAH Metabolic Enzyme rs2295633 G/G 1 1 1 1MGLL Metabolic Enzyme rs604300 G/G 1 1 1 0.5 GABRA2 Transporter/Receptorrs279826 G/G 1 1 1 1 GABRA2 Transporter/Receptor rs279858 C/C 1 1 1 1GABRA2 Transporter/Receptor rs279871 C/C 1 1 1 1 GABRA2Transporter/Receptor rs279826- G/C/C 1 1 1 0.75 rs279858- rs279871MAPK14 Signaling rs12199654 A/A 1 1 1 1 MAPK14/CNR1 Signalingrs12199654- A/A/T/C 1 1 1 0.5 rs12720071 NRG1 Signaling rs17664708 C/C 11 1 1 AKT1 Signaling rs1130233 C/T 1 1 0.5 1 HTR1A Transporter/Receptorrs6295 C/G 1.5 1 1 1 HTR2A Transporter/Receptor rs7997012 G/G 1 1 1.22 1PTGS2 Metabolic Enzyme rs20417 C/C 1 1 1 1

TABLE 9 Calculated dosage and ratio for examples (see FIG. 4 andassociated text) Body Weight Genetic Genetic Cannabis Cannabis BodyAdjust- CBD/THC Test Test Dependence Dependence Final Final DosageWeight ment Standard Adjusted Adjusted Adjusted Adjusted Ratio DosageConditions (mg) (lb) (D1) Ratio (R1) CBD (C3) THC (T3) CBD (C4) THC (T4)(R_(f)) (D_(f)) Insomnia 0.5-20  181-190 9.5 16:1 12.6 1.0 13.4 0.1 9913.5 Anxiety/ 10-100 181-190 57 20:1 76.3 4.7 80.3 0.7 123 81.0Depression Pain 10-100 181-190 57  4:1 64.1 19.6 80.9 2.8 29 83.7

TABLE 10 Variants showing statistically significant association withpain. rs2501432(Genotype): rs6311(Genotype): Group C/C(freq) C/T(freq)T/T(freq) Group C/C(freq) C/T(freq) T/T(freq) Pain 4(0.333) 8(0.667)0(0.000) Pain 5(0.455) 6(0.545) 0(0.000) No pain 1(0.333) 0(0.000)2(0.667) No pain 1(0.333) 0(0.000) 2(0.667) Fisher's p value is 0.006772Fisher's p value is 0.010876 Pearson's p value is 0.006738 Pearson's pvalue is 0.010832

TABLE 11 Genetic variants and their functions and impact on CBD/THCdosage identified from saliva samples 1002 and 1013. Sample ID GenesGene Family SNPs Alleles Brief Functional Description 1002 CNR1Transporter and rs806371 T/G CNR1 Variant: Associated with a reducedresponse to drug-based Receptor Genes treatments for depression and lessresponsive to THC. 1002 GA8RA2 Transporter and rs279826- G/C/C GABRA2Variant: Associated with increased risk of alcohol and THC ReceptorGenes rs279858- dependence. rs279871 1002 COMT Metabolic Enzyme rs4680G/G COMT Variant: Associated with increased risk of exhibitingTHC-induced Genes cognitive impairment that may result in sleepdisorders and/or anxiety. 1002 CYP2C9 Metabolic Enzyme rs28371674 T/TCYP2C9 Variant: Associated with a decrease in metabolizing certain Genesdrugs and THC, leading to an increase persistence of THC in the body.1002 FAAH Metabolic Enzyme rs324420 C/A FAAH Variant: Associated withincreased risk for substance use Genes disorders. 1002 PTGS2 MetabolicEnzyme rs20417 G/G PTGS2 Variant: May lead to enhanced neuropsychiatricand cognitive Genes side effects of THC exposure 1013 HTR2A Transporterand rs6311 C/T HTR2A Variant: Less responsive to anti-depressants andTHC. Receptor Genes 1013 CNR1 Transporter and rs806368 T/T CNR1 Variant:Associated with response to drug-based treatments for Receptor Genesdepression, 1013 CNR1 Transporter and rs806368- T/T/T/T CNR1 Variant:Associated with the risk of the reduced efficacy in Receptor Genesrs806371 antidepressant and cannabis treatment(s). 1013 CNR2 Transporterand rs35761398 C/C CNR2 Variant: Reduced receptor activity and mayincrease the risk of Receptor Genes depression and alcohol dependence.1013 CNR2 Transporter and rs2501432 C/C CNR2 Variant: Reduced receptoractivity and may increase the risk of Receptor Genes depression andalcohol dependence. 1013 NRG1 Signaling Genes rs17664708 C/T NRG1Variant: Associated with certain levels of substance dependence. 1013AKT1 Signaling Genes rs1130233 C/T AKT1 Variant: Associated with lowertolerances to THC. 1013 CYP2C9 Metabolic Enzyme rs1057910 A/C CYP2C9Variant: Associated with a decrease in metabolizing certain Genes drugsand THC, leading to an increase persistence of THC in the body. 1013MGLL Metabolic Enzyme rs604300 G/G MGLL Variant: Associated withincreased risk for substance use Genes disorders.

TABLE 12 Number of CBD/THC dosage relevant variants identified fromdifferent participant samples. Metabolic Saliva Sample Enzyme SignalingTransporter and Grand ID Genes Genes Receptor Genes Total 1002 4 2 61003 3 6 9 1004 3 3 6 1005 2 1 4 7 1006 3 1 6 10 1007 2 1 3 6 1008 4 1 611 1012 3 9 12 1013 2 2 5 9 1014 1 4 5 1015 3 1 3 7 1016 3 1 7 11 1017 21 6 9 1018 3 2 7 12 1019 3 1 11 15 1020 3 5 8 1021 2 1 4 7 1022 3 1 4 81023 2 2 5 9

What is claimed as new and desired to be protected by Letters Patent is:1. A method of providing a personalized cannabinoid treatment regimen toa patient, the method comprising: obtaining two or more base values,wherein each of the base values is a different one of the following: a)a base dosage for a first cannabinoid; b) a base dosage for a secondcannabinoid; c) a base dosage for a combination of the first and secondcannabinoids; or d) a base ratio of the first and second cannabinoids;for each of a plurality of single nucleotide polymorphisms (SNPs) in aselected set of SNPs, obtaining, from a genetic test of the patient, agenotype for the SNP; for each of the SNPs in the selected set of SNPs,obtaining, for the obtained genotype of the SNP, at least one weightingvalue which reflects, for the obtained genotype of the SNP, one or moreresponses selected from the following: i) a response to the first andsecond cannabinoids; ii) a response to the first cannabinoid only; iii)a response to the second cannabinoid only; or iv) cannabinoiddependency; modifying the two or more base values based on the obtainedweighting values to produce two or more regimen values, wherein each ofthe regimen values is a different one of the following: a) a regimendosage for the first cannabinoid; b) a regimen dosage for the secondcannabinoid; c) a regimen dosage for a combination of the first andsecond cannabinoids; or d) a regimen ratio of the first and secondcannabinoids; and treating the patient using the first and secondcannabinoids according to the two or more regimen values.
 2. The methodof claim 1, wherein the first cannabinoid is cannabidiol (CBD) and thesecond cannabinoid is Δ⁹-tetrahydrocannabinol (THC).
 3. The method ofclaim 1, further comprising obtaining a condition for treatment, whereinthe selected set of SNPs comprises a plurality of SNPs associated withthe condition.
 4. The method of claim 3, wherein a value of at least oneof the base values is dependent on the condition.
 5. The method of claim3, wherein the condition is selected from pain, depression, anxiety,fear, sleep disorder, insomnia, energy metabolism disorder,inflammation, neuroprotection, Alzheimer's disease, Huntington'sdisease, Parkinson's disease, emesis, gastrointestinal disorder,cardiovascular disorder, cancer, nausea, vomiting, epilepsy, psychosis,diseases of the basal ganglia, neurodegenerative diseases, autoimmunedisorder, retinal diseases, arthritis, convulsions, neoplastic diseases,or any combination thereof.
 6. The method of claim 1, wherein modifyingthe two or more base values comprises modifying at least one of the basevalues by multiplying the at least one of the base values by a productof at least one of the weighting values for each of a plurality of theSNPs.
 7. The method of claim 1, wherein obtaining at least one weightingvalue comprises obtaining the weighting values for each of the followingresponses individually: i) the response to the first and secondcannabinoids, ii) the response to the first cannabinoid only; iii) theresponse to the second cannabinoid only, or iv) the cannabinoiddependency.
 8. The method of claim 7, wherein modifying the two or morebase values comprises modifying at least one first value, selected fromthe two or more base values, using the weighting values for a first oneof the responses to produce at least one first intermediate value;modifying at least one second value, selected from the two or more basevalues and the at least one first intermediate value, using theweighting values for a second one of the responses to produce at leastone second intermediate value; modifying at least one third value,selected from the two or more base values, the at least one firstintermediate value, and the at least one second intermediate value,using the weighting values for a third one of the responses to produceat least one third intermediate value; and modifying at least one fourthvalue, selected from the two or more base values, the at least one firstintermediate value, the at least one second intermediate value, and theat least one third intermediate value, using the weighting values for afourth one of the responses to produce at least one of the regimenvalues.
 9. The method of claim 1, wherein obtaining the two or basevalues comprises determining the two or more base values using at leastone factor selected from patient weight, condition for treatment,patient age, patient gender, patient body type, other medications takenby patient, or results of a patient blood test.
 10. A system forproviding an individualized cannabinoid treatment regimen, the systemcomprising: a processor configured to perform actions to produce theindividualized cannabinoid treatment regimen, the actions comprising:obtaining two or more base values, wherein each of the base values is adifferent one of the following: a) a base dosage for a firstcannabinoid; b) a base dosage for a second cannabinoid; c) a base dosagefor a combination of the first and second cannabinoids; or d) a baseratio of the first and second cannabinoids; for each of a plurality ofsingle nucleotide polymorphisms (SNPs) in a selected set of SNPs,obtaining, from a genetic test of the patient, a genotype for the SNP;for each of the SNPs in the selected set of SNPs, obtaining, for theobtained genotype of the SNP, at least one weighting value whichreflects, for the obtained genotype of the SNP, one or more responsesselected from the following: i) a response to the first and secondcannabinoids; ii) a response to the first cannabinoid only; iii) aresponse to the second cannabinoid only; or iv) cannabinoid dependency;and modifying the two or more base values based on the obtainedweighting values to produce two or more regimen values, wherein each ofthe regimen values is a different one of the following: a) a regimendosage for the first cannabinoid; b) a regimen dosage for the secondcannabinoid; c) a regimen dosage for a combination of the first andsecond cannabinoids; or d) a regimen ratio of the first and secondcannabinoids.
 11. The system of claim 10, wherein the first cannabinoidis cannabidiol (CBD) and the second cannabinoid isΔ⁹-tetrahydrocannabinol (THC).
 12. The system of claim 10, wherein theactions further comprise obtaining a condition for treatment, whereinthe selected set of SNPs comprises a plurality of SNPs associated withthe condition.
 13. The system of claim 10, wherein modifying the two ormore base values comprises modifying at least one of the base values bymultiplying the at least one of the base values by a product of at leastone of the weighting values for each of a plurality of the SNPs.
 14. Thesystem of claim 10, wherein obtaining at least one weighting valuecomprises obtaining the weighting values for each of the followingresponses individually: i) the response to the first and secondcannabinoids, ii) the response to the first cannabinoid only; iii) theresponse to the second cannabinoid only, or iv) the cannabinoiddependency.
 15. The system of claim 14, wherein modifying the two ormore base values comprises modifying at least one first value, selectedfrom the two or more base values, using the weighting values for a firstone of the responses to produce at least one first intermediate value;modifying at least one second value, selected from the two or more basevalues and the at least one first intermediate value, using theweighting values for a second one of the responses to produce at leastone second intermediate value; modifying at least one third value,selected from the two or more base values, the at least one firstintermediate value, and the at least one second intermediate value,using the weighting values for a third one of the responses to produceat least one third intermediate value; and modifying at least one fourthvalue, selected from the two or more base values, the at least one firstintermediate value, the at least one second intermediate value, and theat least one third intermediate value, using the weighting values for afourth one of the responses to produce at least one of the regimenvalues.
 16. A non-transitory processor readable storage media thatincludes instructions for producing an individualized cannabinoidtreatment regimen, wherein execution of the instructions by one or moreprocessors cause the one or more processors to perform actions,comprising: obtaining two or more base values, wherein each of the basevalues is a different one of the following: a) a base dosage for a firstcannabinoid; b) a base dosage for a second cannabinoid; c) a base dosagefor a combination of the first and second cannabinoids; or d) a baseratio of the first and second cannabinoids; for each of a plurality ofsingle nucleotide polymorphisms (SNPs) in a selected set of SNPs,obtaining, from a genetic test of the patient, a genotype for the SNP;for each of the SNPs in the selected set of SNPs, obtaining, for theobtained genotype of the SNP, at least one weighting value whichreflects, for the obtained genotype of the SNP, one or more responsesselected from the following: i) a response to the first and secondcannabinoids; ii) a response to the first cannabinoid only; iii) aresponse to the second cannabinoid only; or iv) cannabinoid dependency;modifying the two or more base values based on the obtained weightingvalues to produce two or more regimen values, wherein each of theregimen values is a different one of the following: a) a regimen dosagefor the first cannabinoid; b) a regimen dosage for the secondcannabinoid; c) a regimen dosage for a combination of the first andsecond cannabinoids; or d) a regimen ratio of the first and secondcannabinoids.
 17. The non-transitory processor readable storage media ofclaim 16, wherein the first cannabinoid is cannabidiol (CBD) and thesecond cannabinoid is Δ⁹-tetrahydrocannabinol (THC).
 18. Thenon-transitory processor readable storage media of claim 16, wherein theactions further comprise obtaining a condition for treatment, whereinthe selected set of SNPs comprises a plurality of SNPs associated withthe condition.
 19. The non-transitory processor readable storage mediaof claim 16, wherein obtaining at least one weighting value comprisesobtaining the weighting values for each of the following responsesindividually: i) the response to the first and second cannabinoids, ii)the response to the first cannabinoid only; iii) the response to thesecond cannabinoid only, or iv) the cannabinoid dependency.
 20. Thenon-transitory processor readable storage media of claim 19, whereinmodifying the two or more base values comprises modifying at least onefirst value, selected from the two or more base values, using theweighting values for a first one of the responses to produce at leastone first intermediate value; modifying at least one second value,selected from the two or more base values and the at least one firstintermediate value, using the weighting values for a second one of theresponses to produce at least one second intermediate value; modifyingat least one third value, selected from the two or more base values, theat least one first intermediate value, and the at least one secondintermediate value, using the weighting values for a third one of theresponses to produce at least one third intermediate value; andmodifying at least one fourth value, selected from the two or more basevalues, the at least one first intermediate value, the at least onesecond intermediate value, and the at least one third intermediatevalue, using the weighting values for a fourth one of the responses toproduce at least one of the regimen values.